Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators

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Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Hatch, Gary E.
Title Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators
Date 1977-03
Description Two classes of agents have effects on the chemotactic response of human neutrophils. Chemoattractants, such as E. coli bacterial factor (BF) and the recently discovered N-formylmethionyl peptides, initiate directed cellular movement, while chemotactic modulators enhance or depress cell movement initiated by chemoattractans. We have previously shown that cyclic adenosine 3',5'-monophosphate (cAMP) depresses neutrophil migration toward E. coli BF, while cyclic guanosine 3',5'-monophosphate (cGMP) enhances the same process. In the present study, we examined the effects of chemoattractants and modulators on neutrophil levels of cGMP and cAMP. A simplified radioimmunoassay procedure was developed which employed a rapid heat inactivation of cellular samples rather than the traditional acid inactivation. Three chemoattractants and six chemotactic modulators were tested in concentrations which initiate or modulate cell movement. The chemoattractants, BF, N-formylmethionylalanine, and trypsinized human complement, stimulated the accumulation of neutrophil cGMP (40-70% average increase) but had little effect on cAMP concentrations. The enhancing chemotactic modulators, phenylephrine, prostaglandin F1-alpha, carbachol, and phorbol myristate acetate, also caused significant (p ? 0.05) increases (19-34%) in neutrophil cGMP levels without affecting cAMP concentrations. In contrast, two agents which inhibit the chemotactic response; isoproterenol and prostaglandin E1, significantly elevated cAMP concentrations in these cells. These results suggest that the ability to elevate cGMP is inherent in the action of both chemoattractants and enhancing chemotactic modulators. Increases in cAMP appear to be correlated with inhibition of chemotaxis.
Type Text
Publisher University of Utah
Subject Cyclic Compounds
Subject MESH Neutrophils; Nucleotides, Cyclic; Chemotaxis, Leukocyte
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators." Spencer S. Eccles Health Sciences Library. Print version of "Cyclic nucleotide changes in human neutrophils: induced by chemoattractants and chemotactic modulators." available at J. Willard Marriott Library Special Collection. QD 3.5 1977 H38.
Rights Management © Gary E. Hatch.
Format Medium application/pdf
Format Extent 987,505 bytes
Identifier undthes,5037
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Grants from the National Institutes of Health (GM00153, AM18354, AL 13150, and AM16330) and from the Howard Huges Medical Institute (Dr.Hill).
Master File Extent 987,561 bytes
ARK ark:/87278/s6w097q9
Setname ir_etd
ID 191080
Reference URL https://collections.lib.utah.edu/ark:/87278/s6w097q9