HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Werner, C. G. Articles by Pryzwansky, K. B. Search for Related Content PubMed PubMed Citation Articles by Werner, C. G. Articles by Pryzwansky, K. B.

Neutrophil Dysfunction in Guanosine 3',5'-Cyclic Monophosphate-Dependent Protein Kinase I-Deficient Mice¹

Claudia G. Werner^2,*, Virginia Godfrey, Roland R. Arnold, Gerald L. Featherstone, Diane Bender, Jens Schlossmann^*, Matthias Schiemann, Franz Hofmann^* and Katherine B. Pryzwansky

^* Institut für Pharmakologie und Toxikologie, Technische Universität München, München, Germany; Department of Pathology and Laboratory Medicine, and Dental Research Center, Department of Diagnostic Sciences, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599; and Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, München, Germany

The regulation of neutrophil functions by Type I cGMP-dependent protein kinase (cGKI) was investigated in wild-type (WT) and cGKI-deficient (cGKI^–/–) mice. We demonstrate that murine neutrophils expressed cGKI. Similar to the regulation of Ca²⁺ by cGKI in other cells, there was a cGMP-dependent decrease in Ca²⁺ transients in response to C5a in WT, but not cGKI^–/– bone marrow neutrophils. In vitro chemotaxis of bone marrow neutrophils to C5a or IL-8 was significantly greater in cGKI^–/– than in WT. Enhanced chemotaxis was also observed with cGKI^–/– peritoneal exudate neutrophils (PE-N). In vivo chemotaxis with an arachidonic acid-induced inflammatory ear model revealed an increase in both ear weight and myeloperoxidase (MPO) activity in ear punches of cGKI^–/– vs WT mice. These changes were attributable to enhanced vascular permeability and increased neutrophil infiltration. The total extractable content of MPO, but not lysozyme, was significantly greater in cGKI^–/– than in WT PE-N. Furthermore, the percentage of MPO released in response to fMLP from cGKI^–/– (69%) was greater than that from WT PE-N (36%). PMA failed to induce MPO release from PE-N of either genotype. In contrast, fMLP and PMA released equivalent amounts of lysozyme from PE-N. However, the percentage released was less in cGKI^–/– (60%) than in WT (90%) PE-N. Superoxide release (maximum velocity) revealed no genotype differences in responses to PMA or fMLP stimulation. In summary, these results show that cGKI down-regulates Ca²⁺ transients and chemotaxis in murine neutrophils. The regulatory influences of cGKI on the secretagogue responses are complex, depending on the granule subtype.

This article has been cited by other articles:

				V. C. Ganta and J. S. Alexander Focus on carbon monoxide: a modulator of neutrophil oxidants and elastase spatial localization? Am J Physiol Heart Circ Physiol, September 1, 2009; 297(3): H902 - H904. [Full Text] [PDF]

				E. C. Rericha and C. A. Parent Steering in Quadruplet: The Complex Signaling Pathways Directing Chemotaxis Sci. Signal., June 3, 2008; 1(22): pe26 - pe26. [Abstract] [Full Text] [PDF]

				M. Nanamori, J. Chen, X. Du, and R. D. Ye Regulation of Leukocyte Degranulation by cGMP-Dependent Protein Kinase and Phosphoinositide 3-Kinase: Potential Roles in Phosphorylation of Target Membrane SNARE Complex Proteins in Rat Mast Cells J. Immunol., January 1, 2007; 178(1): 416 - 427. [Abstract] [Full Text] [PDF]