In ischemia-reflow states ofcoronary artery disease, the activation of PMN precedes the initiation of tissue damage. Release of atrial natriuretic peptide (ANP) from myocytes occurs within minutes after the onset of myocardial ischemia, which suggests a possible role of ANP in PMN activation. To investigate this possibility, we tested the effects of ANP on functions of PMN in vitro. ANP is a potent signal for priming the PMN respiration burst to secrete superoxide anion. Phorbol 12-myristate 13-acetate, opsonized zymosan, or FMLP could all be used as triggering stimuli to demonstrate the priming of PMN activation by ANP. Only ANP fragments 1-28 and 7-28 enhanced respiration burst activity but identical preparations of ANP fragments 13-18 or 1-11 failed to do so. This structureactivity relationship is typical of receptors for ANP found in other tissues. In addition, ANP stimulated the release oft-glucuronidase from PMN triggered by FMLP. The observed inhibition by ANP of FMLP-stimulated chemotaxis of PMN may be due to their enhanced adhesiveness. These data show that a classic cardiac hormone is involved in regulating important functional activities of PMN. These data support the possibility that ANP could act as a preinflammatory substance in ischemia-reperfusion states and myocardial necrosis. (J. Clin. Invest. 1992Invest. . 89:1580Invest. -1586
Growth hormone (GH) plays an important role in the development, maintenance and function of the immune system. Previous data has demonstrated that GH is also a newly defined macrophage-activating factor. Activation of polymorphonuclear neutrophils (PMN) by GH has not yet been examined. This paper presents studies demonstrating the effects of GH on the migratory behaviour and respiratory burst of PMN. In a modified Boyden chamber chemotaxis assay, GH did not stimulate PMN locomotion when added directly to the cells but potently inhibited formylpeptide-stimulated chemotaxis with effective concentrations in the picomolar range. The migration inhibition observed is known from studies on PMN priming-factors to be due to enhanced adhesiveness of PMN to artificial surfaces such as nitrocellulose, suggesting that GH stimulates PMN adhesiveness. Priming of PMN by GH was confirmed by direct demonstration of a stimulatory effect on reduction of nitroblue tetrazolium. These findings suggest that GH may be involved in the regulation of PMN functions.
Growth hormone, prolactin and somatostatin are polypeptide hormones of the neuroendocrine and peripheral nervous systems. In vitro, these have opposing effects on cells of the immune system. We compared the effects of these peptides on activation of neutrophils using a recombinant preparation of human growth hormone, human prolactin and octreotide, a long acting analog of somatostatin. In the absence of growth hormone, octreotide did not affect either neutrophil locomotion or respiratory burst. Octreotide, however, significantly antagonized growth hormone-induced activation of neutrophils for enhanced respiratory burst as well as growth hormone-induced inhibition of stimulated migration. As the effect of growth hormone on neutrophils is mediated by the prolactin receptor, its inhibition by octreotide was also tested using prolactin as priming agent. Data indicate comparable effects of octreotide on priming of neutrophils by prolactin. The effect of octreotide was dose-dependent and appeared to be selective, as activation of neutrophil respiration burst by gamma-interferon, and inhibition of stimulated migration by tumor necrosis factor-alpha were unaffected by octreotide. The present study suggests that octreotide may act on neutrophils directly by antagonizing growth hormone or prolactin at the cellular level.
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