Non-immunological Stimulation

Di Luzio (1976) established the criteria for an agent which would function as a macrophage stimulant as follows  

Induced macrophage response, i.e., hyperfunc-tion-hyperplasia and hypertrophy of RES - must be reversible in nature 

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While the pools of Ca required (cellular or extracellular) distinguish non-immunologic peptide secretagogues from the classic immunologic secretagogues, peptide (non-immunologic) stimulation of the mast cell differs form IgE-dependent (immunologic) stimulation in a number of other important ways [86a] ... 

Fig. 175. Non-immunologically stimulated peritoneal macrophages from a SPF-NMRl mouse 48 h after a single intraperitoneal injection of 150 mg isotactic polyacrylic acid (Vi 2329 molecular mass 8-12 kDa cf. Muck et al. 1977) as sodium salt per kg body weight. The produced ascites were centrifuged for 10 min at 1000 r.p.m. and incubated in TCM 199 -I- 20 % foetal calf serum on a plastic cover slip for 2 h, rinsed with phosphate buffered saline after Dulbecco and fixed in 1 % glutaraldehyde in 0.07 M phosphate buffer (pH 7.4). Ethanol, amyl acetate. Critical point drying. Gold coating. Cambridge Stereoscan 150 operated at 19 kV. APh-R. 101/80, negative 03 773. (from Schiller 1982)...

The relatively slow phosphorylation of the 78 kDa band in response to either peptide stimulation or to the addition of DSCG suggests that this particular protein band may be involved in the termination of non-immunologically activated secretion [211-214],... 

In addition to IgE-dependent stimulation, mast cells may be activated for mediator release by non-immunological secretagogues such as neuropeptides, anaphylatoxins and xenobiotics, including morphine. 

Another postulated non-immunologic mechanism responsible for LMW-induced OA may involve activation of the alternate complement pathway with subsequent increased production of anaphylatoxins (C3a, C5a), which then could stimulate release of bioactive mediators from mast cells. This possible mechanism has been reported in a few workers with red cedar OA but has not been substantiated for other causative agents of OA (Chan-Yeung, 1982). 

Nitric oxide may induce deleterious effects when airway epithelial or immunological cells are exposed to mineral particles (asbestos, quartz). These particles also stimulate cells to produce NO in large quantities, but pulmonary cells are unable to destroy these particles, and a non-physiologically excess production of NO results, perhaps causing tissue damage due to a reaction of NO with cellular macromolecules. 

Sera from levamisole-treated mice, rabbits and man were found to yield a dialyzable, complement-unrelated serum factor which did not contain any levamisole metabolites, but which could simulate the biologic effects of levamisole itself. 162 This factor enhanced carbon clearance,169 stimulated lymphocyte proliferation in vitro,187 restored immunological reactivity of athymic mice,179 induced in vitro maturation of mouse pre-T cells,179 stabilized tumor remission and reduced tumor load in experimental systems.162 The factor could not be detected in mice which failed to respond to treatment with levamisole but non-responders reacted to serum factor in a similar way as responders treated with levamisole itself.162 a perhaps identical serum factor could also be induced by the sulfhydryl compound diethyl-dithiocarbamate (65).1 which appears to share some of the immunoenhancing and immunorestorative properties of levcimisole if administered in... 

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