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Growth hormone inhibits normal B-cell differentiation and neutrophils' chemotaxis in vitro
M C Fornari1, M P Scolnik, M F Palacios
1IO/IIHEMA Academia Nacional de Medicina, Buenos Aires, Argentina.
Abstract:
In acromegalic patients we have previously described a low ability of B-lymphocytes to differentiate into plasma cells under PWM stimulation, and a decreased chemotaxis of polymorphonuclear leukocytes (PMN) towards N-formylmethionylphenilalanine (FMP). In this study we examined the effect of exogenous GH over these immune functions in normal cells. PMN were purified by dextran sedimentation, incubated with recombinant human GH (0 to 20 ng/ml) and subjected to stimulation with FMP. PBMC were cultured with or without PWM, in the presence of GH (between 0 and 100 ng/ml). Plasma cells were determined as hemolysis plaque forming cells and also by immunofluorescence. GH, in a dose-dependent way, decreased directed migration of PMN (5 ng/ml: 1.787 +/- 148 microns; 10 ng/ml: 1.581 +/- 221 microns; 20 ng/ml: 1.569 +/- 149 microns, all as mean +/- S.E.M.), when compared to similar values of untreated PMN (0 ng/ml 2.085 +/- 139 microns). GH treatment did not modify spontaneous migration. Net migration showed the same pattern as directed migration. GH decreased dose-dependently the PWM-driven differentiation of B-lymphocytes into plasma cells to 60% of the basal level. Although not significantly, GH tended to increase spontaneous B-cell differentiation. These results could account for the already described defect in B-cell differentiation and PWN chemotaxis in acromegaly, emphasizing the relationship between the endocrine and immune systems.
Insights
Growth hormone (GH) impairs immune cell function. Exogenous GH reduces B-lymphocyte differentiation into plasma cells and decreases polymorphonuclear leukocyte (PMN) migration, potentially explaining immune defects in acromegaly.
Area of Science:
- Endocrinology
- Immunology
- Cell Biology
Background:
- Acromegaly patients exhibit impaired B-lymphocyte differentiation and reduced polymorphonuclear leukocyte (PMN) chemotaxis.
- The influence of exogenous growth hormone (GH) on these specific immune functions in normal cells requires investigation.
Purpose of the Study:
- To investigate the direct effects of exogenous recombinant human GH on B-lymphocyte differentiation and PMN chemotaxis in normal individuals.
- To determine if GH can replicate the immune dysfunctions observed in acromegaly.
Main Methods:
- Purified PMN were incubated with varying concentrations of GH and stimulated with N-formylmethionylphenilalanine (FMP) to assess chemotaxis.
- Peripheral blood mononuclear cells (PBMCs) were cultured with or without pokeweed mitogen (PWM) and GH to quantify plasma cell differentiation via hemolysis plaque assays and immunofluorescence.
Main Results:
- GH significantly decreased PMN directed migration in a dose-dependent manner.
- Exogenous GH also dose-dependently reduced PWM-stimulated B-lymphocyte differentiation into plasma cells, lowering it to 60% of basal levels.
- GH did not alter spontaneous PMN migration but showed a trend towards increasing spontaneous B-cell differentiation.
Conclusions:
- Exogenous GH negatively impacts key immune cell functions, specifically B-cell differentiation and PMN chemotaxis.
- These findings suggest that elevated GH levels, as seen in acromegaly, may directly contribute to the observed immune system defects.
- The study highlights the intricate relationship between the endocrine system (GH) and immune system function.