摘要:

AbstractI have asked myself many times why I agreed to become the Editor‐in‐Chief of theJournal of Leukocyte Biology.It is a timeconsuming, at times contentious and hazardous position with the potential to lose friends and make enemies.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.1

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractAll cells of the hematopoietic system have finite life spans, shorter by far than that of the host. They end their lives by committing a form of cellular suicide or programmed cell death. The morphology of this process is considerably different from that of necrosis and is called apoptosis. Apoptotic cells undergo a stereotyped sequence of changes, including shrinkage and nuclear collapse. The cell is quickly recognized and eaten by a phagocyte, without the elicitation of an inflammatory response. Although most cells have specific triggers of apoptosis, the killer T cell seems able to induce apoptosis in any cell it recognizes. The process of apoptosis is regulated by cytokines, and may be modulated both in vitro and in vivo.J. Leukoc. Biol.57: 2–10; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.2

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractTen years ago, a new field emerged with the isolation and cloning of tumor necrosis factor (TNF), an exceptionally pleiotropic cytokine that seemed to promise an effective treatment for cancer. The field drew a heavy following from the existing disciplines of immunology, oncology, endocrinology, hematology, and infectious disease research as it was recognized that the actions of TNF were relevant to each. The first International Congress on TNF and Related Cytokines was held in Heidelberg in 1986, and subsequent congresses were held in Napa, Chiba, and Veldhoven. This, the 5th Congress, was held at the Asilomar Conference Center in Monterey.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.11

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractMetchnikoff first described mononuclear phagocytic cells at the end of the last century and proposed their critical involvement in the host immune defense. Since then, an impressive body of literature has documented the involvement of monocytes in the immune response as immunomodulating cells [1, 2], antigen‐presenting cells [3], and effector cells [1, 4–7]. Human monocytes can be induced to express new or augmented biological functions in a process generally referred to as activation. The expression of the activated phenotype in monocytes is transient and, in contrast to that of other immune cells such as lymphocytes or natural killer (NK) cells, it is not associated with proliferation. Monocyte proliferation, occurring primarily in the bone marrow [8–10], maintains an adequate supply of circulating monocytes ready to extravasate to the tissues in response to physiological or pathological stimuli. The recognition that proliferation is not part of the genetic program of monocyte activation poses interesting questions about the function and biology of growth factor receptors on these cells. Monocytes express receptors for a variety of growth factors that are either monocyte lineage specific, such as the macrophage colony‐stimulating factor (CSF‐1) receptor [11, 12]; shared with other cell lineages, such as the granulocyte‐macrophage CSF (GM‐CSF) receptor [13]; or typical of other lineages, such as the interleukin‐2 receptor (IL‐2R) [14–16]. However, monocytes respond to stimulation by growth factors not with proliferation but with functional changes. Two remarkable examples are CSF‐1 and IL‐2. CSF‐1 induces proliferation of monocyte precursors in the bone marrow [17], but it promotes survival [18], migration [19], cytokine secretion [20], and cytotoxic responses [21]in circulating monocytes. IL‐2, originally described as a T cell growth factor [22], is a powerful activator of human monocytes. Fresh human monocytes respond to IL‐2 with microbicidal [23]and tumoricidal activities [1, 4–7], cytokine [24–28]and growth factor [29–31] production, and expression of growth factor receptors [21, 32]. We will discuss the effects of IL‐2 on human monocytes, the differential expression and modulation of the IL‐2R subunits, and their relationship with the responsiveness of monocytes to IL‐2. Finally, we will briefly discuss the regulation of IL‐2–induced monocyte activation by inhibitory signals. IL‐2 can also activate murine macrophages. However, we will limit our discussion to the human monocyte system. 33–35], tumor necrosis factorα(TNF‐α) [25, 28], interleukin‐6 (IL‐6) [26], and interleukin‐8 (IL‐8) [27]. TNF‐αand IL‐βare inflammatory mediators cytotoxic or cytostatic for tumor cells, whose involvement in the acute‐phase response and in monocyte antitumor activity has been reviewed [36–38]. Monocytes are the predominant source of IL‐6 and IL‐8 in peripheral blood [26, 39], although other cell types contribute to the IL‐6 and IL‐8 levels [26, 40–42]. IL‐8 induces chemotaxis in basophils, neutrophils, and T lymphocytes [43–47]and is member of the family of chemoattractant cytokines now called chemokines (for a review see ref. 48). IL‐6 is a pleiotropic cytokine whose biological activities include regulation of the acute‐phase response [37, 49], stimulation of multipotent colony formation of hematopoietic stem cells [50], induction of immunoglobulin production [51], and induction of T cell growth and cytotoxic T lymphocyte differentiation [52, 53]. IL‐8 and IL‐6 induction by IL‐2 occurs at the transcriptional level. The promoter of both genes contains a consensus sequence for the nuclear transactivator complex NF‐χB [54, 55]. The observation that IL‐2 increases the expression of NF‐χB complexes in the nucleus of monocytes suggests that NF‐χB may be involved in the transcriptional activation of IL‐8 and IL‐6 genes by IL‐2 (T. Musso et al., unpublished observation). Secretion of IL‐6 and IL‐8 is a specific response to IL‐2 and not a general response to activating stimuli, because interferon‐γ (IFN‐γ), which is also a potent monocyte activator, inhibits rather than induces IL‐6 or IL‐8 production [26, 27]. IL‐2 stimulates IL‐6 and IL‐8 production both directly and indirectly by inducing IL‐1βand TNF‐αsecretion, which, in turn, stimulates the expression of IL‐8 and IL‐6 [26, 56]. The indirect response to IL‐2 represents an amplifying loop that is delayed with respect to direct stimulation and that may be important in allowing prolonged production of IL‐6 or IL‐8 during an inflammatory response.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.13

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractLeukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the role of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat (SHR), the number of circulating leukocytes and their level of activation are significantly increased compared with its normotensive control, the Wistar‐Kyoto rat (WKY). We have demonstrated that elevated levels of glucocorticoid in SHR suppress P‐selectin–mediated leukocyte‐endothelial interaction in the microcirculation. It is possible that the disturbance in leukocyte‐endothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate the contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy and investigating the effect of hydrocortisone. In addition, we have studied by immuno‐histochemistry the expression of the endothelial adhesion molecule, P‐selectin, in response to histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY. The elevated blood pressure, above‐normal leukocyte counts, and elevated number of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine‐induced leukocyte‐endothelial interaction in the mesenteric venules of SHR was restored after adrenalectomy. Treatment with hydrocortisone significantly attenuated the elevated leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P‐selectin expression in SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal leukocyte‐endothelial interaction in response to an inflammatory stimulation in SHR is abolished after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives.J. Leukoc. Biol.57: 20–26; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.20

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractNitric oxide (NO), a potent and versatile free radical, is synthesized in macrophages and mast cells as well as in other types of cells by the inducible form of nitric oxide synthase (iNOS). In this study, cells containing iNOS were identified in the uteri of cycling mice by using a rabbit antibody generated to an iNOS‐specific peptide. Macrophages were identified in semiserial sections of the same tissues with the monoclonal antibody, F4/80, and mast cells were identified by toluidine blue staining. In tissue sections of uteri obtained from mice in the four stages of the estrous cycle (8 to 11 mice per stage), iNOS immunoreactivity was strongest in diestrus‐I uteri and weakest in diestrus‐II uteri. Myometrial mast cells and endometrial epithelial cells were prominent locations of iNOS, and specific protein was also present in myometrial smooth muscle and macrophage‐like cells in the endometrial stroma. Because cyclic variations suggested regulation of iNOS expression by ovarian steroid hormones, studies were done using ovariectomized mice. Seven days after ovariectomy, immunoreactive iNOS was low but detectable in mast cells and luminal epithelial cells. In the uteri of ovariectomized, estradiol‐17β(E2)–treated mice, mast cells were iNOS+after 24 h whereas epithelial cells were negative; the reverse was observed in progesterone (P4)‐treated mice. Both mast cells and epithelial cells were iNOS+in the uteri of mice that had received a combination of E2+ P4. These results indicate that several types of uterine cells produce iNOS and that expression of this enzyme in specific cell lineages is governed by ovarian steroid hormones. The data are consistent with the postulate that NO derived from uterine leukocytes and other types of cells plays a role in uterine cyclicity and preparation for pregnancy.J. Leukoc. Biol.57: 27–35; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.27

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractAn antirat monoclonal antibody (mAb) against inducible nitric oxide synthase (iNOS), ANOS11, was used for immunohistochemistry to examine the expression of iNOS in various organs and tissues of adult rats in experimental endotoxic shock induced by lipopolysaccharide (LPS) injection. The phenotype of iNOS‐expressed cells was also examined immunohistochemically using various mAbs. In control rats, very few cells were positive for ANOS11 except in the thymus. After intravenous injection of LPS, the number of iNOS‐positive cells increased rapidly in almost all organs, except the thymus and brain, peaked 6 h after the injection, and decreased slowly. Of the numerous inflammatory cells that infiltrated the lungs, liver, and spleen after LPS injection, many were positive for ANOS11. Besides inflammatory cells, hepatocytes and endothelial cells of the aorta were also positive for ANOS11 but only around 6 h after injection. The cellular composition of iNOS‐positive infiltrated cells changed along with the progression of endotoxic shock. At 4 to 6 h after injection, most iNOS‐positive cells were considered polymorphonuclear leukocytes judging by their positive reactivity to 0X42 and their nuclear morphology. The population of iNOS‐positive macrophages positive for EDI or ED2 increased with time. After 24 h, many iNOS‐positive macrophages were found around the focal necrosis in the liver and spleen. These results indicate that the expression of iNOS in neutrophils, endothelial cells, and hepatocytes precedes that of macrophages in experimental endotoxic shock. The expression of iNOS in various cells and organs is closely associated with the progress and pathological changes of endotoxic shock.J. Leukoc. Biol.57: 36–44; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.36

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe time course of endothelial P‐selectin, ICAM‐1, and E‐selectin expression was studied in a feline model of myocardial ischemia and reperfusion. Cats were subjected to 90 min of myocardial ischemia followed by 0, 10, 20, 60, 150, or 270 min of reperfusion. At the end of reperfusion, the coronary vasculature was examined immunohistochemically to localize monoclonal antibodies (mAbs) PB1.3, RR1/1, and Cyl787 directed against P‐selectin, ICAM‐1, and E‐selectin, respectively. Immuno‐histochemical localization for P‐selectin, recognized by mAb PB1.3, was maximally expressed 20 min after reperfusion in 60 ± 6% of coronary venules (P<0.05 compared to non‐reperfused controls), and covered 59 ± 3% of the endothelial cell perimeter of immunostained coronary venules. Immunolocalization of mAb PB1.3 gradually declined at 60, 150, and 270 min of reperfusion. Immunohistochemical localization of mAb RR1/1 (anti‐ICAM‐1) in endothelial cells of coronary venules was observed to a modest extent in non‐ischemic myocardium and at 10, 20, and 60 min of reperfusion, but was significantly increased following 150 and 270 min of reperfusion (P<0.05 compared non‐reperfused controls). At 270 min post‐reperfusion, mAb RR1/1 was seen in 50 ± 4% of coronary venules. Endothelial immunolocalization of mAb Cyl787 (anti‐E‐selectin) was only observed in 13 ± 1 and 14 ± 3% of coronary venules after 150 and 270 min of reperfusion, respectively, suggesting that pronounced expression of E‐selectin does not occur within 270 min after reperfusion. These results demonstrate sequential expression of three major endothelial cell adherence molecules in situ following myocardial ischemia and reperfusion. The timing of endothelial cell expressed P‐selectin and ICAM‐1 could coordinate neutrophil trafficking during the early stages of reperfusion.J. Leukoc. Biol.57: 45–55; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.45

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractWe have previously shown that increased resistance toSalmonella enteritidisorgan infectivity in day‐old chicks was conferred by the immunoprophylactic administration ofS. enteritidis‐immunc lymphokines (ILK). This resistance was associated with a significant increase in the number of circulating heterophils 4 h after ILK injection. The objective of the present study was to evaluate heterophil function following the administration of ILK in day‐old chicks. Significant increases (P<0.001) in adherence, chemotaxis, and phagocytosis ofS. enteritidiswere found with heterophils isolated from ILK‐injected chickens compared to the heterophils isolated from birds injected with either pyrogen‐free saline or lymphokines from non‐immune T cells. After phagocytosis, the heterophils from the ILK‐injected chickens were also able to kill significantly greater numbers ofS. enteritidismore rapidly than did the heterophils from the saline‐injected control birds (within 30 min, control cells killed 21.89% of the bacteria whereas ILK‐treated cells killed 88.22%). We also found that the heterophils from the ILK‐injected birds were more efficient killers ofS. typhimurium, S. gallinarum,andE. coliThese results strongly suggest that the protection againstS. enteritidisorgan invasion induced by the prophylactic treatment of day‐old chicks with ILK involves activated heterophils which migrate rapidly to the inflammatory stimulus where they phagocytize and kill the bacteria.J. Leukoc. Biol.57: 56–62; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.56

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe 27E10 antigen is a heterodimer of MRP8 and MRP14, two Ca2+‐binding proteins related to the S‐100 protein family. Previous studies have shown that 27E10 epitope–bearing monocyte subsets are prevalent in early acute but absent in chronic inflammatory conditions. These observations further provide an impetus for identifying the cellular mechanisms responsible for the appearance of different monocyte subpopulations during inflammation. Therefore this in vitro study was carried out to investigate the influence of adhesion in inducing 27E10‐positive subsets. In adhesion assays the role of 27E10 antigen in spontaneous adherence was obvious, as a monoclonal antibody directed against the 27E10 antigen significantly inhibited the adherence of monocytes to collagen and fibronectin. In contrast, these extracellular matrix (ECM) proteins induce the cell surface expression and association of 27E10 antigen with cytoskeleton (CSK), detected by flow cytometry and confocal laser scan microscopy, respectively. Similar results were obtained on cross‐linking with specific antibodies, thus showing involvement of the integrin molecules VLA‐2 and VLA‐4. In addition, the association with CSK could be confirmed by differential detergent extraction. The observed redistribution of 27E10 antigen guided by collagen compared with fibronectin was also paralleled by an augmented release of inflammatory cytokines interleukin‐6, tumor necrosis factorα, and superoxide anions. Thus, this study demonstrates that under inflammatory conditions the interactions of extravasating monocytes with the ECM may induce an activated phenotype of monocytes marked by 27E10.J. Leukoc. Biol.57: 63–71; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.63

出版商:Wiley    

年代:1995

数据来源: WILEY