In monocytes

Weber KS, von Hundelshausen P, Clark-Lewis 1, Weber PC, Weber C (1999) Differential immobilization and hierarchical involvement of chemokines in monocyte arrest and transmigration on inflamed endothelium in shear flow. Eur J Immunol 29(2) 700-712 Wesselingh SL, Power C, Glass JD, Tyor WR, McArthur JC, Farber JM, Griffin JW, Griffin DE (1993) Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia. Ann Neurol 33(6) 576-582... 

Parada CA, Roeder RG (1996) Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain. Nature 384(6607) 375-378 Peluso R, Haase A, Stowring L, Edwards M, Ventura P (1985) A Trojan Horse mechanism for the spread of visna virus in monocytes. Virology 147(1) 231-236 Peng G, Greenwell-Wild T, Nares S, Jin W, Lei KJ, Rangel ZG, Munson PJ, Wahl SM (2007) Myeloid differentiation and susceptibility to HIV-1 are linked to APOBEC3 expression. Blood 110(l) 393-400... 

Ingestion ofL. monocytogenes can cause abortion in humans and animals and in the case of listeriosis a prime characteristic is an increase in monocytes. 

Sun W, Wang G, Zhang ZM, Zeng XK, Wang X. Chemokine RANTES is upregu-lated in monocytes from patients with hyperhomocysteinemia. Acta Pharmacol Sin 2005 26(11) 1317—1321. 

Schwartz D, Andalibi A, Chaverri-Almada L, et al. Role of the GRO family of chemokines in monocyte adhesion to MM-LDL-stimulated endothelium. J Clin Invest 1994 94(5) 1968-1973. 

Umehara H, Goda S, finai T, et al. Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1. Immunol Cell Biol 2001 79(3) 298-302. 

A wide range of cells are capable of producing IL-l (Table 9.4). Different cell types produce the different IL-ls in varying ratios. In fibroblasts and endothelial cells, both are produced in roughly similar ratios, whereas IL-ip is produced in larger quantities than IL-la in monocytes. Activated macrophages appear to represent the major cellular source for IL-1. 

Pineda-Zavela, A.P. et al., Nitric oxide and superoxide anion production in monocytes from children exposed to arsenic and lead in region Lagunera, Mexico, Toxicol. Appl. Pharmacol. 198, 283, 2004. 

Regulation of expression may occur at both the transcriptional and post-transcriptional levels. The mRNA for GM-CSF contains (in common with those of some other cytokines) conserved regulatory sequences in the 3 untranslated region, which may affect its rate of translation. The gene is constitutively transcribed in monocytes, endothelial cells and fibroblasts, but the mRNA is unstable and so does not accumulate to levels sufficient to allow translation into significant amounts of protein. Activation of these cells results in the increased expression of GM-CSF protein, which arises from both an enhanced rate of transcription (as detected in nuclear runoff experiments) and also an increased stability of the mRNA, perhaps by mechanisms analogous to those described above during activation of G-CSF expression ( 2.2.3.1). 

Cathepsin G, a cationic, glycosylated protein of relative molecular mass -27 kDa, exists in four isoforms (25-29 kDa) that are identical in amino acid sequence but differ in levels of glycosylation. It is a component of azurophilic granules and present in human neutrophils at 1.5-3 jug/106 cells, but at lower levels in monocytes. cDNA has been cloned and sequenced (and the amino acid sequence predicted), and the gene has been localised to chromosome 14ql 1.2. The gene comprises five exons and four introns, a structure similar to that of the elastase gene. 

These forms of human FcyRII are differentially expressed in immune cells. For example, FcyRIIB transcripts are detectable in monocytes, macrophages and lymphocytes, but not in neutrophils, NK cells or T-cell lines. On the other hand, FcyRIIA and FcyRIIC are expressed on monocytes, macro-... 

In vivo administration of y-interferon to atypical X-CGD patients also led to improvements in monocyte and neutrophil respiratory-burst activity and killing, and in some cases spectroscopically-detectable cytochrome b has been observed (occasionally present at up to 50% of normal levels). This improvement followed two subcutaneous doses (0.1 mg/m2) on consecutive days and lasted for up to a month. Because TNF can act synergisti-cally with y-interferon in increasing the expression of the heavy chain of cytochrome b, perhaps the combined use of y-interferon with TNF or some other cytokine(s) will prove even more beneficial. 

Infection is the most common cause of morbidity and mortality in MDS patients, accounting for 40-60% of deaths in various studies. The common infections are those normally associated with neutropenias, such as Gramnegative septicaemia and bacterial bronchopneumonias. Indeed, most MDS patients are neutropenic at some stage in their disease. Even those who do not have a neutropenia may have a defect in their neutrophil function. Many patients have clearly-defined defects in T- and B-lymphocyte functions, and variable defects in monocyte numbers or function have been described. Disorders of neutrophil function are common. Many reports indicate that phagocytosis, chemotaxis, respiratory-burst activity and degranulation are defective in some MDS patients, and hypogranulation is often observed. 

Newborn healthy infants vary in their total leukocyte counts from 9,000 to 30,000 per cu. mm., in neutrophils from 6,000 to 26,000, in eosinophils from 20 to 850, in basophils from 0 to 640, in lymphocytes from 2,000 to 11,000, and in monocytes from 400 to 3,100. In healthy adults the total leucocytes vary from 3,500 to 14,800, which may be distributed within the following ranges ... 

Janabi, M., Yamashita, S., Hirano, K., Sakai, N., Hiraoka, H., Matsumoto, K., Zhang, Z., Nozaki, S., and Matsuzawa, Y., 2000, Oxidized LDL-induced NF-kappa B activation and subsequent expression of proinflammatory genes are defective in monocyte-derived macrophages from CD36-deficient patients, Arteriosc/er. Thromb. Vase. Biol. 20 1953-1960. 

Lee ES, Sarma D, Zhou H, Henderson AJ (2002) CCAAT/enhancer binding proteins are not required for HIV-1 entry but regulate proviral transcription by recruiting coactivators to the long-terminal repeat in monocytic cells. Virology 299 20-31... 

In monocytes stimulated with Toll-like receptor-triggering bacterial products, histamine inhibits the production of proinflammatory IL-1-like activity, TNF-a, IL-12 and IL-18, but enhances IL-10 secretion, through HR2 stimulation [26, 69]. Histamine also downregulates CD 14 expression via Hj receptors on human monocytes [70]. The inhibitory effect of histamine via Hj receptor appears through the regulation of ICAM-1 and B7.1 expression, leading to the reduction of innate immune response stimulated by LPS [71]. 

Liposome-encapsulated immunomodulators are currently under investigation in different patient groups although this development has certainly not advanced as far as that with the liposomal anthracyclines. MLV-MTP-PE (multilamellar vesicles-muramyl tripeptide-phos-phatidylethanolamine) was studied in several clinical trials in osteosarcoma patients who developed pulmonary metastases during adjuvant chemotherapy [108], The intravenous administration of MLV-MTP-PE induced tumouricidal properties in monocytes as well as increase in serum IL-1 shortly after intravenous infusion. Furthermore elevations in C-reactive protein, 32-microglobulin and ceruloplasmin were frequently observed. Even higher anti-tumour activity was observed in combination with ifosfamide. These preliminary results suggests that liposome-encapsulated immunomodulators in combination with chemotherapy may be an appropriate treatment for recurrent disease. 

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