Reduced PMN beta 2 integrins after trauma: a possible role for colony-stimulating factors.
The beta 2 integrins are composed of a common 95-kD beta-subunit (CD18) and one of three possible alpha-subunits: CD11a, CD11b, or CD11c. These molecules are involved in neutrophil adhesion, diapodesis, chemotaxis and phagocytosis. In this study, the effects of traumatic injury on neutrophil expression of these alpha-subunits were investigated. Neutrophils from patients with severe trauma (n = 30) were stained with fluorescent anti-CD11a, -CD11b, or -CD11c. The percentage of positive neutrophils and the mean channel fluorescence were assayed by flow cytometry. In 10 patients and 10 normals, the effects of granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on alpha-subunit expression were evaluated. Ninety-four +/- 2% (s.e.m.) of normal neutrophils were CD11a+, 89 +/- 1% were CD11b+ and 89 +/- 8% were CD11c+. Only 65 +/- 2% of patient neutrophils were CD11a+, 45 +/- 5% were CD11b+ and 8 +/- 1% were CD11c+. Culture of normal neutrophils without colony-stimulating factors resulted in reduced expression of CD11a and CD11c, but up-regulation of CD11b. Down-regulation of CD11a and CD11c was partially reversed by colony-stimulating factors (30 U/ml). CD11b receptor density was further up-regulated by GM-CSF and G-CSF. Treatment of patient neutrophils with colony-stimulating factors in culture resulted in up-regulation of alpha-subunits as well. GM-CSF appeared to have the greater effect. These results indicate that colony-stimulating factors may have a clinical role in improving beta 2 integrin expression, and suggest a use in these infection-prone patients.
White-Owen
C
C
Department of Surgery, University of Cincinnati College of Medicine, OH 45267-0558.
Hartmann
S
S
Alexander
J W
JW
Babcock
G F
GF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D002478:Cells, Cultured; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D016023:Integrins / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology*; D014947:Wounds and Injuries / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D016023:Integrins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor