title: Intracellular signalling during neutrophil recruitment.
abstract: Recruitment of leucocytes such as neutrophils to the extravascular space is a critical step of the inflammation process and plays a major role in the development of various diseases including several cardiovascular diseases. Neutrophils themselves play a very active role in that process by sensing their environment and responding to the extracellular cues by adhesion and de-adhesion, cellular shape changes, chemotactic migration, and other effector functions of cell activation. Those responses are co-ordinated by a number of cell surface receptors and their complex intracellular signal transduction pathways. Here, we review neutrophil signal transduction processes critical for recruitment to the site of inflammation. The two key requirements for neutrophil recruitment are the establishment of appropriate chemoattractant gradients and the intrinsic ability of the cells to migrate along those gradients. We will first discuss signalling steps required for sensing extracellular chemoattractants such as chemokines and lipid mediators and the processes (e.g. PI3-kinase pathways) leading to the translation of extracellular chemoattractant gradients to polarized cellular responses. We will then discuss signal transduction by leucocyte adhesion receptors (e.g. tyrosine kinase pathways) which are critical for adhesion to, and migration through the vessel wall. Finally, additional neutrophil signalling pathways with an indirect effect on the neutrophil recruitment process, e.g. through modulation of the inflammatory environment, will be discussed. Mechanistic understanding of these pathways provide better understanding of the inflammation process and may point to novel therapeutic strategies for controlling excessive inflammation during infection or tissue damage.
authors.affiliation: Department of Physiology, Semmelweis University School of Medicine, Tűzoltó utca 37-47, 1094 Budapest, Hungary MTA-SE 'Lendület' Inflammation Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, 1094 Budapest, Hungary mocsai.attila@med.semmelweis-univ.hu.
authors.forename: Attila
authors.initials: A
authors.lastname: Mócsai
authors.affiliation: Department of Cardiovascular Physiology and Pathophysiology, Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, 80336 Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Walzog
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
mesh_terms: D000818:Animals; D006801:Humans; D020556:Neutrophil Infiltration; D044042:Receptors, Formyl Peptide / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration
chemical_list: D044042:Receptors, Formyl Peptide; D016028:Receptors, Leukocyte-Adhesion
keywords: Inflammation; Leucocytes; Migration; Neutrophils; Signalling