Blood monocytes

A new generation of antiinflammatory agents having immunosuppressive activity has been developed. The appearance of preclinical and clinical reports suggest that these are near entry to the pharmaceutical market. For example, tenidap (CP-66,248) (12) has been demonstrated to inhibit IL-1 production from human peripheral blood monocytes in culture (55). Clinically, IL-1 in synovial fluids of arthritic patients was reduced following treatment with tenidap. Patients with rheumatoid or osteoarthritis, when treated with tenidap, showed clinical improvement (57,58). In addition to its immunological effects, tenidap also has an antiinflammatory profile similar to the classical NSAIDs (59). Other synthetic inhibitors of IL-1 production are SKF 86002 (20) andE-5110 (21) (55). 

White blood cell preferentially located near potential entry sites for microbial pathogens and specialized for the uptake of particulate material by phagocytosis. Most macrophages originate from peripheral blood monocytes and are able to leave the circulation following stimulation by chemotactic agents. 

McElrath MJ, Steinman RM, Cohn ZA (1991) Latent HlV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients. J Clin Invest 87(l) 27-30... 

ROM production by peripheral blood monocytes Production of ROM by peripheral blood monocytes in response to a variety of stimuli is increased in patients with active IBD (Table 10.2), su esting that such cells may respond to local stimulants within the gut more readily than in normal subjects or those with quiescent disease, and so may play a role in perpetuating the inflammatory response, cent studies have su ested that peripheral blood monocytes in Crohn s disease may be primed by the baaerial cell wall products LPS and peptidoglycanpolysaccharide (Muraki et al., 1992). 

Muraki, T., Fu, R.D., Kazoroski, L., Baldassano, R.N., Ber-tovich, M.J., Izutan, R., Schreiber, S., Lichtenstein, G.R., Sartor, R.B. and MacDermott, R.P. (1992). Crohn s disease peripheral blood monocytes are primed by bacterial cell wall products for enhanced oxygen radical production. Gastroenterology 102, A668. 

Okabe, N., Kuriowa, A., Fujita, K., Shibuya, T., Yao, T. and Okumura, M. (1986). Immunolt cal studies on Crohn s disease. (vi) Increased chemiluminescent response of peripheral blood monocytes. J. Clin. Lab. Immunol. 21, 11-15. 

Growing clinical data also points to the importance of IL-8 in atherogenesis. IL-8 has been found in atheromatous lesions from patients with atherosclerotic disease including carotid artery stenosis (103), CAD (118), abdominal aortic aneurysms (AAA) (103,104,114), and peripheral vascular disease (PVD) (104). Furthermore, studies using plaque explant samples have yielded more direct evidence for IL-8 involvement. Media from cultured AAA tissue induced IL-8-dependent human aortic endothelial cell (HAEC) chemotaxis (122). Homocysteine, implicated as a possible biomarker for CAD, is also capable of inducing IL-8 (123-125) by direct stimulation of endothelial cells (123,124) and monocytes (125). When patients with hyperhomocysteinemia were treated with low-dose folic acid, decreases in homocysteine levels correlated with decreases in IL-8 levels (126). Statins significantly decrease serum levels of IL-6, IL-8, and MCP-1, as well as expression of IL-6, IL-8, and MCP-1 mRNA by peripheral blood monocytes and HUVECs (127). Thus, IL-8 may be an underappreciated factor in the pathogenesis of atherosclerosis. 

Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003 19 71-82. 

Mandel JS, Berlinger NT, KayN. 1989. Organophosphate exposure inhibits Non-Specific esterase staining in human blood monocytes. Amer J Industrial Med 15 207-212. 

Nucleic acid extraction protocols using guanidine hydrochloride, sodium sarco-syl, and ethanol have been developed to quantify viral RNA by bDNA in lymph node tissue, liver tissue, and peripheral blood monocytes (Wilber and Urdea, 1995). 

Figure 9.5 Healthy volunteer monocytes after erythrophagocytosis. Rabbit erythrocytes were incubated with heat-inactivated mouse antirabbit erythrocyte serum. Human peripheral blood monocytes (MN) were obtained after Ficoll-Paque isolation and monocyte clumping with subsequent separation from lymphocytes, yielding a 95 % pure MN population. Non-ingested erythrocytes were removed by hypotonic lysis.

Blood monocyte recruitment to site of microvascular damage... 

Recruited blood monocytes encountering local elevated levels of Ap peptide would then refold the Ap into a fibrillar conformation, thus forming the core of an NP adjacent to a blood vessel [24]. These plaque-bound monocytes differentiate into macrophages and mount an aberrant "wound response" through the release of neurotrophic and chemotactic agents, inducing an inappropriate ectopic sprouting response toward the... 

Thiele L, Rothen-Rutishauser B, Jilek S et al (2001) Evaluation of particle uptake in human blood monocyte-derived cells in vitro. Does phagocytosis activity of dendritic cells measure up with macrophages J Control Release 76 59-71... 

Pacifici R, Rifas L, Teitelbaum S, Slatopolsky E, McCracken R, Bergfeld M, Lee W, Avioli LV, Peck WA (1987) Spontaneous release of interleukin 1 from human blood monocytes refiects bone formation in idiopathic osteoporosis. Proc Nad Acad Sci USA 84 4616-4620... 

Sakurai, T., Ohta, T., and Fujiwara, K., Inorganic arsenite alters macrophage generation from human peripheral blood monocytes, Toxicol. Appl. Pharmacol., 203, 145, 2005. 

G-CSF expression is controlled at both the transcriptional and posttranscrip-tional levels. A sequence of 300 nucleotides upstream of the initiation codon is conserved in both the murine and human genes, and this appears to contain three regulatory sites. G-CSF (and some other cytokine genes) may be constitutively transcribed by cells such as blood monocytes, fibroblasts and endothelial cells, but the mRNA may be short-lived (fi/2 < 15 min). The mRNA contains poly-AUUUA sequences in the untranslated region, and this motif is usually associated with mRNA instability. Indeed, such regions have also been identified in mRNA for GM-CSF, IL-1, IL-6, interferons, TNF, some growth factors, c-jun, c-fos, c-myc and c-myb. Upon the addi-... 

Further support to the notion that liposomal BPs exert their effects systemically was achieved through the use of liposomes loaded with the fluorescent marker, Rhodamine, with or without a BP (52,69). Marked reduction of the fluorescent signal was observed in blood monocytes (as well as reduced number) and in the liver and spleen of LBP-treated animals. Fluorescent liposomes (FL) were detected in injured but not in intact arteries. FL coadministered with LBPs significantly reduced the fluorescent signal in the injured arterial wall. The inactivation of monocytes after systemic administration of LBPs results in reduction of tissue macrophages in the injured artery. Thus, the outcome of systemic administration was manifested as local treatment for the injured artery. 

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