Lymphokines: Enhancement by Granulocyte-Macrophage and Granulocyte Colony-Stimulating Factors of Neonatal Myeloid Kinetics and Functional Activation of Polymorphonuclear Leukocytes

Abstract

Colony-stimulating factors, such as the granulocyte-macrophage and the granulocyte colony-stimulating factors (GM-CSF and G-CSF), are glycoproteins with biologic specificity defined by their ability to support proliferation and differentiation of hematopoietic cells of various lineages. Their physiologic activities include stimulation and proliferation of early stem cell precursors and functional activation of mature peripheral effector cells. Recently produced recombinant human (rh) GM-CSF and G-CSF have been demonstrated to regulate hematopoietic neutrophil progenitor colony growth; to stimulate the release of bone marrow neutrophil storage pools; and to prime mature effector functions, including chemotaxis, oxidative metabolism, phagocytosis, C3bi receptor expression, and antibody-dependent cytotoxicity in adults. We examined the effects of rh-GM-CSF on priming superoxide release and chemotaxis of neonatal (cord) polymorphonuclear leukocytes (PMNs) and of rh-G-CSF and rh-GM-CSF on bone marrow neutrophil egress in the neonatal rat. A time-response evaluation of the effect of rh-GM-CSF revealed enhanced release of superoxide by PMNs. PMN chemotaxis also was enhanced by rh-GM-CSF, with a maximal response occurring earlier than enhanced superoxide release. Intraperitoneal administration of rh-G-CSF or rh-GM-CSF to 1-day-old rats resulted in significant increases in white blood cell counts and significant early neutrophilia. Bone marrow examination revealed that the neutrophilia was secondary to egress and mild depletion of the neutrophil storage pool but that the neutrophil storage pool later returned to normal. These preliminary studies suggest that rh-GM-CSF and rh-G-CSF prime neonatal effector function and induces significant PMN egress and neutrophilia.(ABSTRACT TRUNCATED AT 250 WORDS)