Genetic Evidence of a Functional Monocyte Dichotomy

Abstract

Human peripheral blood monocytes are found as two distinct populations based upon differential expression of chemokine receptors, adhesion molecules, Fc receptors, and cytokines. cDNA microarray analysis now reveals additional differences between these subsets that suggest dramatically diverse functions. One monocyte subset (CD14++CD16-) appears to be closely paired with neutrophils, and may have as its primary function the removal and recycling of apoptotic neutrophils at sites of inflammation. The other monocyte subset (CD14+CD16+) expresses numerous genes encoding proteins with antimicrobial activity and thus may be more directly involved in peripheral host defense. The production of monocytes capable of efficiently removing dying neutrophils may be necessary to prevent host tissue damage and autoimmune response induction. Therefore, species like humans that produce relatively high levels of circulating neutrophils must also produce relatively high numbers of the recycling monocytes. Conversely, species such as mice and rats that maintain relatively lower levels of circulating neutrophils require fewer recycling monocytes.

Comparative Analysis of Monocyte Subsets in the Pig

“…CSF3 controls the production, differentiation, and function of granulocytes (34), and has also been described as a maturation factor for monocytes (35,36). Production of CD14 hi monocyte subset in the bone marrow may be coordinated with granulocytes (15,37). CD14 hi monocytes in both pig and human share with granulocytes the high expression of S100A8 (5).…”

Expression of intracellular cytokines, HSP72, and apoptosis in monocyte subsets during exertional heat stress in trained and untrained individuals

“…CD14 ϩ CD16 ϩ inflammatory monocytes are intrinsically involved in host defense, responding directly to invading pathogens through their transcription and release of multiple cytokines, promoting initiation of the acute phase response. In contrast, CD14 ϩϩ classic monocytes primarily act as scavengers, aiding in the neutralization of unbound LPS (65,86) and removal of apoptotic cells as part of the mononuclear phagocyte system (46). At rest, a majority of the CD14 ϩ CD16 ϩ monocytes are not present in the peripheral circulation but reside in the marginal pool and are released into the peripheral circulation via catecholaminemediated sympathetic mechanisms (78).…”

“…PERIPHERAL BLOOD MONOCYTES play an important role in protection against invading pathogens and activation of innate immunity (46). Based on differential expression of antigenic markers CD14 [part of the LPS receptor, CD14/Toll-like receptor (TLR-4)/MD-2] and CD16 (Fc␥RIII), monocytes can be divided into two phenotypically and functionally distinct subsets (82,90).…”

“…The bulk of monocytes are defined as classic monocytes and are strongly positive for surface receptor CD14 (CD14 ϩϩ CD16 Ϫ ), whereas the minor subset are referred to as inflammatory monocytes (CD14 ϩ CD16 ϩ ) because of their high capacity to express proinflammatory cytokines such as TNF-␣ (6,62,64,90). Inflammatory monocytes have the ability to respond directly with antimicrobial activity, whereas the classic subset of monocytes act as scavengers, removing apoptotic cells and aiding in the resolution of inflammation (46).…”

A novel flow cytometry‐based assay to study leukocyte–endothelial cell interactions in vitro

“…Although human and mouse monocyte subtypes are similar in their co-expression of chemokine receptors, such as the MCP-1 receptor CCR2 and the fractalkine receptor CX3CR1, there seems to be functional divergence, impeding the direct translation of data gained from mouse models to human disease (9,(12)(13)(14)(15)(16) pos monocytes, have been described (23,24). First, clinical reports imply a relevance of those individual populations in the pathogenesis of atherosclerosis as well as in angiogenesis and in the remodeling process following myocardial or cerebral infarction (1)(2)(3)10,18,22,25,26).…”