The roles of CD11/CD18 and ICAM-1 in acute Pseudomonas aeruginosa-induced pneumonia in mice.
Neutrophil accumulation in response to Pseudomonas aeruginosa in the lungs is mediated through CD11/CD18. This study determined the roles of CD11a, CD11b, and intercellular adhesion molecule (ICAM)-1 in P. aeruginosa-induced pneumonia and compared the function of ICAM-1 using Abs or ICAM-1 mutant mice. Anesthetized BALB/c mice pretreated with either Abs against CD11a, CD11b, ICAM-1, or rat IgG received intratracheal instillation of P. aeruginosa for 4 h. In other studies, ICAM-1 mutant and wild-type mice received either anti-ICAM-1 Ab or rat IgG followed by instillation of P. aeruginosa. The data show that Abs against CD11a, CD11b, and ICAM-1 in BALB/c mice inhibited neutrophil emigration by 79, 81, and 56%, respectively. ICAM-1 mutant mice showed no inhibition of neutrophil emigration compared with wild-type mice. Pretreatment with anti-ICAM-1 Ab inhibited neutrophil emigration in wild-type (129/SvxC57) mice by 67% but had no effect in ICAM-1 mutant mice, suggesting that the Ab was acting specifically through recognition of its Ag. We conclude that CD11a and CD11b are required for neutrophil emigration. The observed function of ICAM-1 varies depending on the method by which it is inhibited. Abs may overestimate function by altering other cellular functions or mutant mice may develop alternative pathways of emigration.
Qin
L
L
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University, Indianapolis 46202, USA.
Quinlan
W M
WM
Doyle
N A
NA
Graham
L
L
Sligh
J E
JE
Takei
F
F
Beaudet
A L
AL
Doerschuk
C M
CM
D000208:Acute Disease; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D018845:CD11 Antigens / Q000502:physiology*; D018821:CD18 Antigens / Q000502:physiology*; D002465:Cell Movement / Q000276:immunology; D004487:Edema / Q000209:etiology / Q000276:immunology; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009504:Neutrophils / Q000276:immunology / Q000502:physiology; D018410:Pneumonia, Bacterial / Q000209:etiology / Q000276:immunology*; D011552:Pseudomonas Infections / Q000209:etiology / Q000276:immunology*; D051381:Rats
D000906:Antibodies; D018845:CD11 Antigens; D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1