Granulocyte colony-stimulating factor reverses septic shock-induced polymorphonuclear leukocyte dysfunction.

BACKGROUND

Polymorphonuclear leukocyte (PMN) function is dependent on normal Fcg receptor expression. Fibronectin and laminin are each capable of modulating the surface expression of CD32w (Fc gamma RII) and CD16 (Fc gamma RIII). Their ability to alter CD64 (Fc gamma RI) expression, however, was unclear; therefore the purpose of these studies was to define the role of CD64 (Fc gamma RI) in modulating PMN oxidative metabolism and degranulation for PMNs adherent to either fibronectin or laminin.

METHODS

Experiments were performed in two phases; initially, PMNs isolated from normal volunteers and adherent to buffer, fibronectin, or laminin were studied. Subsequently, two groups of patients were evaluated; group 1 (n = 8) represents control patients undergoing major intraabdominal procedures. Group 2 (n = 12) represents patients in septic shock from defined sources of intraabdominal infection. Monomeric immunoglobulin G was used as a specific ligand for CD64 followed by measurements of superoxide anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production to measure oxidative metabolism and azurophilic granule degranulation. Six cytokines were then tested to determine their ability to restore biologically active CD64 on group 2 PMNs.

RESULTS

Fibronectin or laminin increased CD64 on PMNs of normal volunteers and group 1 patients. CD64 signal transduction augmented superoxide anion, hypochlorous acid, and N-acetyl-beta-glucosaminidase production by PMNs of volunteers and group 1. Neither fibronectin nor laminin increased CD64 expression on group 2 PMNs. Granulocyte colony-stimulating factor restored both receptor number of CD64 and biologic activity of these receptors on the surface of group 2 PMNs in the presence of fibronectin or laminin.

CONCLUSIONS

Septic shock depresses CD64 expression on the PMN surface. Restoration of this receptor by granulocyte colony-stimulating factor not only augments receptor number but also improves oxidative metabolism and primary granule degranulation in the presence of either fibronectin or laminin.