摘要:

Monocytes are capable of producing a growth factor which causes fibroblasts to replicate in vitro. This macrophage‐derived growth factor (MDGF) may be particularly important in controlling the proliferation of mesenchymal cells in the pulmonary interstitium following acute lung injury. To evaluate the role of macrophages in modulating the proliferative capacity of fibroblasts, we added serum‐free culture medium from lavage‐derived rat lung macrophages to confluent monolayers of quiescent adult rat lung fibroblasts and monitored their return to the cell cycle both by3H‐thymidine incorporation and by increases in cell number. Growth factor activity secreted in 24 h by untreated macrophages was compared to that from normal macrophages stimulated in vitro by bacterial lipopolysaccharide (LPS) and from macrophages retrieved from lungs injured by intratracheal administration of bleomycin. Unstimulated macrophages from control animals secreted minimal amounts of MDGF; addition of LPS to normal macrophages increased MDGF secretion 3‐ to 4‐fold. Adherent cells obtained by lung lavage of bleomycin‐treated animals spontaneously secreted near maximal levels of nondialyzable MDGF with little further stimulation by LPS. The MDGF secreted by LPS‐stimulated control cells and by macrophages retrieved from injured lungs share identical elution profiles from DEAE‐Sepha‐ cel anionic exchange columns, and heat stability profiles. The substance acts as a competence factor when tested on rat lung fibroblasts. These shared physical and biologic properties suggest that the growth factor secreted by cells lavaged from injured lungs is identical to MDGF secreted in response to LPS. Because MDGF release could not be induced by direct exposure of freshly isolated macrophages to bleomycin, we suggest that augmented release of MDGF is an indirect feature of acute lung injury in this model.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.1

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Mononuclear cell fibroblast interactions in the normal human lung are poorly understood. Mononuclear cells can regulate fibroblast function and blood monocytes are known to migrate to the lung and participate in pulmonary inflammation. Thus, to clarify mononuclear cell‐fibroblast interactions in the normal lung, we obtained supernatants from adherent monocytes and characterized their effect on the log phase growth of human lung fibroblasts. Monocyte supernatants inhibited fibroblast growth in a dose‐dependent fashion. The inhibition was the result of an approximately 16,000 MW soluble factors) that was heat stable, trypsin sensitive, and chymotrypsin resistant. Elaboration of the factors) required monocyte protein synthesis and was not restricted to a density‐defined monocyte subpopulation. The inhibitory capacity of a monocyte supernatant was directly related to its ability to stimulate fibroblast prostaglandin production. Blocking fibroblast prostaglandin production reversed the inhibition of fibroblast growth caused by monocyte supernatants. Thus, monocyte inhibition of fibroblast growth may be mediated by fibroblast prostaglandin production. Recruitment of monocytes to the lung and subsequent monocyte inhibition of fibroblast growth may be important in regulating pulmonary fibrosis.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.15

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Broncho‐alveolar cells lavaged from the lungs of 1‐ and 7‐day‐old piglets and adult pigs were examined to determine their alveolar macrophage content, cell size, and ability to phagocytyze emulsified oil droplets and to chemiluminesce in response to opsonized zymosan particles. Alveolar macrophages were identified by specific cytochemical stains and differential cell counts as being 95%, 97%, and 90% of the cell populations, respectively. The cell volume of macrophages from 1‐day‐old pigs was 383 ± 40 µm3; while the cell volumes from 7 day and adult pigs were 1,660 ± 265 and 1,411 ± 310µm3. Alveolar macrophage from 1‐day‐old piglets possessed little ability to engulf oil droplets; however, macrophages from 7‐day‐old piglets phagocytized these opsonized droplets at a rate equivalent to alveolar macrophages obtained from adult pigs. The phagocytosis of oil droplets by both 7‐day and adult alveolar macrophages manifested similar characteristics. Both rates can be described by saturation kinetics, and while temperatures from 37° to 30°C had little effect, the rate declined rapidly between 30° and 16°C. Alveolar macrophages from 1‐day‐old piglets displayed a lower magnitude of chemiluminescence than cells from 7‐ day‐old and adult pigs and did not always respond to zymosan exposure. On the other hand, 7‐day‐old and adult pig alveolar macrophages were quite similar in their ability to chemiluminesce. Increasing extracellular glucose from 1 to 20 mM induced a concomitant increase in chemiluminescence. The findings suggest that functionally competent alveolar macrophages emerge in the pig lung approximately 1 week after birth.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.29

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Fructose‐1,6‐diphosphate (FDP) exerts a marked activity on reticuloendothelial system (RES) functions, increasing in mice the clearance of colloidal carbon. ATP depletion occurring during phagocytic activity is concentrated by FDP.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.45

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Hypothermia may be associated with compromised host defenses and serious bacterial infections in man. We have examined the effects of moderate hypothermia (29°C) on neutrophil function in vitro. At 29°C, neutrophil phagocytosis of Staphylococcus aureus was impaired. In contrast, neutrophil killing of Streptococcus faecalis was most affected by hypothermia. Phagocytosis, as measured by neutrophil ingestion of opsonized oil‐red‐O‐particles, was reduced at 29°C over the 15 min of observation. Neutrophil metabolism linked to bactericidal pathways dependent on oxidative metabolism was reduced at 29°C. Hexose monophosphate pathway (HMP) activity in neutrophils early after stimulation with latex particles was reduced. After 2 hr HMP activity was similar at 29°C and 37°C. Neotetrazolium dye reduction was reduced early after latex stimulation of neutrophils and after 30 min it was similar to cells at 37°C. Leukocyte migration under agarose to bacterial‐derived and formyl‐methionyl‐ phenylalanine chemotactic factors was reduced by 50% and 70%, respectively. Migration to serum‐derived chemotactic factor was reduced by only 20%. When cells were cooled to 29°C for 30 to 90 min and rewarmed, neutrophil function was normal. These effects of hypothermia on neutrophil function may explain, in part, the increased incidence of serious and frequently fatal bacterial infections in man.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.51

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

The potential mechanisms involved during the faster release of [125l]‐iodo‐2′‐ deoxyuridine (125ldUrd)‐labeled target sarcoma cells in the presence of normal C57BL/6J peritoneal macrophages were investigated. Maximum (= 90%) “spontaneous” release of125l from target cells cultured alone occurred over a period of about 10 days. However, after about 3 days, confluent sheets of target cells developed. In the presence of normal macrophages, 90% of the125l was released between 3 and 7 days, again with the formation of confluent sheets of target cells. This enhanced125I release was not influenced by increasing the relative concentration of IdUrd using the nonradioactive isotope127ldUrd. Established mechanisms of target cell destruction were investigated but no evidence was found for the involvement of superoxide anion, hydrogen peroxide, or regulation by prostaglandin synthesis. The macrophage‐mediated effect was abrogated by incorporating hydrocortisone‐acetate (10−7to 10−4M) into the culture medium but this did not affect target cell proliferation. The use of serum‐free culture medium suggested that macrophages secreted a soluble mediator that was not derived from or dependent on the presence of fetal bovine serum. In addition, macrophage‐conditioned medium was able to induce the faster125l release. The failure to precipitate with 20% trichloroacetic acid the125l released from target cells cultured in the presence of macrophages indicated that the radioactive component had been separated from the precipitable DNA. The data are discussed in light of two possible hypotheses: that macrophages recognized subtle changes in IdUrd‐labeled cells and exacerbate radiotoxicity, and that the faster release reflected proliferative death caused by stimulated growth.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.63

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

This study was designed to examine the inducibility and lineage of nonspecifi‐ cally cytotoxic effector cells in the hamster spleen. Employing a known T cell mitogen, concanavalin A (ConA), and a monoclonal antibody against a recently identified hamster T cell marker (Thy 1.2 homologue), we examined the effector cells induced in spleen by ConA and the role of T cells in regulating this response. Cytotoxicity was measured against uninfected baby hamster kidney cells, cells infected with herpes simplex virus, or a mouse target, SV3T3, in a 16‐hr51Cr release assay. Pretreatment of spleen cells with ConA (2.5–10µg ConA/ml) markedly augmented killing of all targets. Although ConA pretreatment of effector cells enhanced cytotoxicity, pretreatment of targets did not, indicating that ConA is acting at the effector cell level. Supernatants from ConA‐stimulated spleen cells also augmented spleen lymphoctye cytotoxicity, suggesting that the ConA effect is mediated by lym‐ phokines (LK). Depletion of Thy 1.2‐positive cells from the spleen cells failed to influence augmentation of cytotoxicity by either ConA or ConA‐induced LK, indicating that the precursor cells are not T cells. However, depletion of Thy 1.2‐positive cells completely eliminated the production of LK in response to ConA, indicating that the factors in LK that augment cytotoxicity are strictly T cell dependent. Whether nonspecific cytotoxic cells induced by ConA in the absence of T cells and by the T cell LK are the same population is not known. None of the cytotoxicity induced from intact or T cell‐depleted spleen cells by either ConA or LK expressed the Thy 1.2 homologue. These results suggest that nonspecific cytotoxic lymphocytes of non‐T cell lineage in the hamster are regulated via both T cell‐dependent and T cell‐independent mechanisms.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.75

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

We compared survival and the intensity of bronchoalveolar inflammation reflected by lung lavage after the intraperitoneal injection of endotoxin from Escherichia coli serotype 055B5 in rats breathing air and those breathing 60% oxygen for six days after endotoxin injection. Survival following 7.5 mg/kg of endotoxin was comparable in air‐breathing rats (50%) and in oxygen‐breathing rats (63%). Endotoxin caused a dose‐dependent increase in the recovery of polymorphonuclear leukocytes from the lung. Oxygen breathing reduced the percentage of neutrophils recovered by lavage 24 hr after endotoxin from 17% to 9% after 2.5 mg/kg of endotoxin and from 34% to 12% after 7.5 mg/kg of endotoxin. The absolute number of neutrophils recovered was also significantly decreased in oxygen‐breathing rats. The activity of pulmonary angiotensin‐ converting enzyme (ACE) has been reported to be affected by oxygen tension, and ACE degrades bradykinin, a proinflammatory mediator. Therefore, we questioned whether the salutary effect of increased inspired oxygen tension on the magnitude of neutrophil influx into the airspaces could be related to changes in ACE activity. We found that after 48 hr of peroral pretreatment of the rats with captopril, a specific ACE inhibitor, there was increased recovery of neutrophils by lavage 24 hr after injection of endotoxin in air‐breathing rats. Captopril pretreatment also increased the chemotactic activity of bronchoalveolar lavage fluid (BALF). There was no concomitant alteration in the accumulation of125l albumin in the lung following captopril pretreatment either in endotoxin‐treated rats or in controls. Thus, breathing 60% oxygen decreased the accumulation of neotrophils in airspaces after intraperitoneal endotoxin injection and pharmacologic inhibition of ACE had the opposite effect. Alterations in the activity of pulmonary angiotensin‐converting enzyme related to alveolar oxygen tension is a potential speculative mechanism for modulation of alveolar inflammation by the inspired oxygen concentration in this model.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.87

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

Thromboembolic complications are known in cancer patients after i.v. administration of Corynebacterium parvum. We examined the ability of this organism to induce production of procoagulant activity by human blood mononuclear leukocytes in vitro. After 4 hours incubation Corynebacterium parvum was an effective stimulant for mononuclear leukocytes, behaving in the same way as the typical gram‐negative bacterium Escherichia coli, whereas mononuclear cells incubated with Staphylococcus aureus were not affected. Corynebacterium parvum used was found devoid of endotoxin by the Limulus assay and was not affected by Polymyxin B, which, on the contrary, inhibited Escherichia coli‐induced production of procoagulant activity. Intact Corynebacterium parvum may be required for the production of procoagulant activity and, although this specific aspect of the research will require further study, from the exposed data it is concluded that such a production could be a factor contributing to the pathogenesis of the coagulopathy following Corynebacterium parvum therapy.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.101

出版商:Wiley    

年代:1985

数据来源: WILEY

摘要:

During an acute nonspecific inflammatory reaction initiated in the pleural cavity by a nondiffusible stimulus (calcium pyrophosphate crystals), the oxidative metabolism, as measured by chemiluminescence and superoxide release, of cells harvested from both the inflammatory site and at points distant from it was studied.The oxidative metabolism of peritoneal macrophages, obtained from rats undergoing an inflammatory reaction (pleurisy), demonstrated a transient decrease in activity compared with the resident population when using both zymosan and phorbol myristate acetate as stimulants. This metabolic unresponsiveness induced by inflammation may be related to the concomitant changes in the levels of prostacyclin in the peritoneal cavity. It should be emphasized that the peritoneal cellular composition or number did not change during these events. On the other hand alveolar macrophages from inflamed animals showed no significant changes in their superoxide production or chemiluminescence compared to controls. The precise reason for these inflammation‐induced changes is unknown; however the acute nonspecific inflammatory reaction was able to modulate the oxidative metabolism of cells not only at the site of inflammation, but at points distant from it.

ISSN:0741-5400    

DOI:10.1002/jlb.37.1.109

出版商:Wiley    

年代:1985

数据来源: WILEY