Enhancement of peritoneal leukocyte function by granulocyte colony-stimulating factor in rats with abdominal sepsis

• Published in: Critical care medicine Vol. 26; no. 2; p. 315
• Main Authors: Zhang, P, Bagby, G J, Stoltz, D A, Summer, W R, Nelson, S
• Format: Journal Article
• Language: English
• Published: United States 01.02.1998
• Subjects: Abdomen; Animals; CD18 Antigens - analysis; CD18 Antigens - drug effects; Disease Models, Animal; Drug Evaluation, Preclinical; Granulocyte Colony-Stimulating Factor - therapeutic use; Integrin alphaXbeta2 - analysis; Integrin alphaXbeta2 - drug effects; Macrophage-1 Antigen - analysis; Macrophage-1 Antigen - drug effects; Male; Neutrophils - drug effects; Neutrophils - immunology; Peritoneal Cavity - cytology; Phagocytosis - drug effects; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Sepsis - immunology; Sepsis - therapy; Specific Pathogen-Free Organisms; Time Factors
• ISSN: 0090-3493
• DOI: 10.1097/00003246-199802000-00035

To investigate the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and peritoneal neutrophils during intra-abdominal sepsis. Placebo, controlled study, using a rat model of intra-abdominal sepsis. Animal research facility. Male specific pathogen-free Sprague-Dawley rats. Abdominal sepsis was produced in rats by cecal ligation and puncture. The control animals received a sham operation. G-CSF (subcutaneous injection at 50 microg/kg) or vehicle (100 microL of 5% dextrose) treatment was initiated at 1 hr after cecal ligation and puncture or sham operation and repeated at 12-hr intervals thereafter. Six hours after cecal ligation and puncture, CD11b/c and CD18 expression on circulating neutrophils was significantly up-regulated when compared with those in the sham operated control animals. Peritoneal neutrophils exhibited a further up-regulation of these adhesion molecules than did the circulating neutrophils. A sustained up-regulation of CD11b/c and CD18 was found in peritoneal neutrophils even at 24 hrs after cecal ligation and puncture. G-CSF treatment increased CD11b/c expression on circulating neutrophils in 6-hr sham-operated rats, but did not further up-regulate CD11b/c or CD18 expression on circulating or peritoneal neutrophils in cecal ligation and puncture rats. Phagocytic activities of circulating neutrophils assessed by uptake of fluorescent latex microspheres were lower in 24-hr cecal ligation and puncture rats when compared with the sham-operated controls. G-CSF treatment prevented this inhibition. Furthermore, G-CSF enhanced the phagocytic activities of peritoneal neutrophils in both 6- and 24-hr cecal ligation and puncture rats when compared with those of the vehicle-treated animals. Spontaneous hydrogen peroxide generation by circulating neutrophils was increased in 6-hr cecal ligation and puncture rats, but not in 24-hr cecal ligation and puncture rats. Peritoneal neutrophils exhibited an inhibition of phorbol myristate acetate-stimulated hydrogen peroxide generation. G-CSF treatment did not up-regulate neutrophil hydrogen peroxide generation. Circulating and peritoneal neutrophils exhibit marked polymorphism in their functional activities during the host response to abdominal sepsis. G-CSF treatment significantly enhanced the phagocytic function of both circulating and peritoneal neutrophils which may be one mechanism underlying its protective effect in abdominal sepsis.