Activation of neutrophils by factors released from alveolar macrophages stimulated with collagen-like polypeptides.
Oxidant-induced injury is associated with breakdown of interstitial collagen and the accumulation of inflammatory cells in the lungs. In previous studies, we demonstrated that phagocyte accumulation is mediated, in part, by chemotactic factors generated from damaged collagen. To determine if alveolar macrophages also mediate the migration of polymorphonuclear leukocytes (PMN) into the lungs, we examined the release of chemotactic factors from alveolar macrophages treated with native or synthetic collagenous peptides. These included fragments of bovine collagen digested with bacterial collagenase (CG) or cyanogen bromide (CB) as well as small molecular weight synthetic polypeptides containing proline (Pro), glycine (Gly), and hydroxyproline (Hyp), the major amino acids that comprise collagen. We found a dose- and time-related generation of PMN chemotactic activity by collagen peptide-treated macrophages. The maximum activity was released 72 h after pretreatment of macrophages for 1 to 3 h with 0.1 to 1 microM CG-, CB-, or (Pro-Pro-Gly)5-peptides. The native peptides derived from CG-digested collagen were more active than synthetic peptides containing Pro and Gly. Neither trypsin digests of bovine serum albumin nor synthetic peptides containing Hyp stimulated chemotactic factor release from macrophages. The alveolar macrophage-derived chemotactic factor was found to lose activity when dialyzed and after heat or trypsin treatment. The release of PMN-activating factors by collagen peptide-treated macrophages was also examined. Alveolar macrophage-conditioned medium was found to stimulate PMN production of reactive oxygen intermediates as well as elastase and gelatinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Laskin
D L
DL
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855-0789.
Soltys
R A
RA
Berg
R A
RA
Riley
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002352:Carrier Proteins; D002634:Chemotaxis, Leukocyte; D003238:Connective Tissue / Q000187:drug effects / Q000293:injuries; D018093:Gelatinases; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000276:immunology*; D010196:Pancreatic Elastase / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology; D051381:Rats
D002352:Carrier Proteins; D011506:Proteins; C007105:c1q-binding proteins; D006861:Hydrogen Peroxide; D010196:Pancreatic Elastase; D010434:Pepsin A; D018093:Gelatinases