Neutrophil adhesion molecule surface expression and responsiveness in cystic fibrosis.
The neutrophil-dominated inflammation of the lung in cystic fibrosis (CF) has traditionally been seen as a physiological response to continuous opportunistic infection. Recent studies suggest, however, that regulation of the inflammatory response itself may be altered in CF. Neutrophil migration from the bloodstream involves alterations in surface expression of the adhesion molecules L-selectin and Mac-1 (CD11b/CD18). The aim of this study was to assess neutrophil adhesion molecule expression and responsiveness in CF. Neutrophils from chronic (n = 16) and acutely infected (n = 13) CF patients and 15 normal control subjects were directly assessed by Fluorescence-activated cell sorter (FACS) analysis for surface expression of L-selectin and CD11b before and after stimulation with interleukin 8 (IL-8) or f-Met-Leu-Phe (fMLP). Neutrophils from stable (n = 5) and acutely infected (n = 5) non-CF bronchiectasis patients were also assessed. Surface upregulation of CD11b was similar in all groups. Basal levels of L-selectin were also comparable among all groups, however, when stimulated, neutrophils from both stable and acutely infected CF patients shed significantly less L-selectin than those from control subjects (p < 0.05 and p < 0.01, respectively). This decreased responsiveness was not observed in either stable or acutely infected non-CF bronchiectasis patients. These results add to the accumulating evidence suggestive of a defective inflammatory response in CF.
Russell
K J
KJ
Department of Medicine and Therapeutics, University College Dublin, Belfield, Ireland.
McRedmond
J
J
Mukherji
N
N
Costello
C
C
Keatings
V
V
Linnane
S
S
Henry
M
M
Fitzgerald
M X
MX
O'Connor
C M
CM
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001987:Bronchiectasis / Q000276:immunology; D018845:CD11 Antigens / Q000235:genetics / Q000276:immunology; D018821:CD18 Antigens / Q000235:genetics / Q000276:immunology; D002465:Cell Movement; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D019041:L-Selectin / Q000235:genetics / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology; D011550:Pseudomonas aeruginosa / Q000276:immunology; D015854:Up-Regulation
D018845:CD11 Antigens; D018821:CD18 Antigens; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine