title: Differential effects of CD18, CD29, and CD49 integrin subunit inhibition on neutrophil migration in pulmonary inflammation.
abstract: Neutrophil migration to lung alveoli is a characteristic of lung diseases and is thought to occur primarily via capillaries rather than postcapillary venules. The role of adhesion molecules CD18 and CD29 on this migration in a mouse model of lung inflammation has been investigated. The number of neutrophils present in bronchoalveolar lavage fluid was determined 4 h after intratracheal instillation of LPS (0.1-1 microg) or murine recombinant KC (CXC chemokine, 0.03-0.3 microg). Both stimuli produced a dose-related increase in neutrophil accumulation. Intravenous anti-mouse CD18 mAb, 2E6 (0.5 mg/mouse), significantly (p < 0.001) attenuated LPS (0.3 microg)- but not KC (0.3 microg)-induced neutrophil accumulation. The anti-mouse CD29 mAb, HM beta 1-1 (0.02 mg/mouse), significantly (p < 0.05) inhibited both LPS (0.3 microg)- and KC (0.3 microg)-induced neutrophil migration. A second mAb to CD18 (GAME-46) and both F(ab')(2) and Fab of HM beta 1-1 produced similar results to those above, while coadministration of mAbs did not result in greater inhibition. Electron microscopy studies showed that CD29 was involved in the movement of neutrophils from the interstitium into alveoli. The effect of mAbs to CD49 (alpha integrin) subunits of CD29 was also examined. mAbs to CD49e and CD49f inhibited both responses, while anti-CD49b and CD49d significantly inhibited responses to KC only. These data suggest that CD29 plays a critical role in neutrophil migration in pulmonary inflammation and that CD49b and CD49d mediate CD18-independent neutrophil accumulation.
authors.affiliation: Cardiovascular Research Group, Division of Clinical Sciences, Northern General Hospital, University of Sheffield, Sheffield, United Kingdom. V.C.Ridger@Sheffield.ac.uk
authors.forename: V C
authors.initials: VC
authors.lastname: Ridger
authors.forename: B E
authors.initials: BE
authors.lastname: Wagner
authors.forename: W A
authors.initials: WA
authors.lastname: Wallace
authors.forename: P G
authors.initials: PG
authors.lastname: Hellewell
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood / Q000276:immunology / Q000502:physiology; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D002464:Cell Migration Inhibition; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D006224:Cricetinae; D016207:Cytokines / Q000008:administration & dosage; D004306:Dose-Response Relationship, Immunologic; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage; D007249:Inflammation / Q000276:immunology; D007275:Injections, Intravenous; D039423:Integrin alpha1; D019012:Integrin beta1 / Q000276:immunology / Q000502:physiology; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D007442:Intubation, Intratracheal; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000276:immunology; D051381:Rats
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D007140:Immunoglobulin Fab Fragments; D039423:Integrin alpha1; D019012:Integrin beta1; D016023:Integrins; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C074302:keratinocyte-derived chemokines