Reduced PMN β2 integrins after trauma: A possible role for colony-stimulating factors

Abstract

The β2 integrins are composed of a common 95-kD β-subunit (CD18) and one of three possible α-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 α-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 α-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 upregulated by GM-CSF and G-CSF. Treatment of patient neutrophils with colony-stimulating factors in culture resulted in up-regulation of α-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 β2 integrin expression, and suggest a use in these infection-prone patients.