Purification of haptoglobin and its effects on lymphocyte and alveolar macrophage responses

Abstract

Clinical observations made on a patient with acute hypersensitivity pneumonitis revealed that the patient's serum contained a mitogenic inhibitor and an extremely high haptoglobin (Hp) level; this led to an investigation of the role of Hp in lymphocyte function. Hp was isolated and purified from acute phase rabbit serum by a new method using DE-52 anion exchange chromatography and preparative isoelectric focusing in a range of pH 3.0-5.0. This technique produced a homogenous, biologically active product in fewer steps and in higher yields than existing techniques. Purified rabbit Hp significantly inhibited polyclonal lymphocyte mitogenic responses to PHA or Con A in a dose-response fashion. Hp also significantly inhibited B-cell mitogenesis at a high concentration (200 mg/100 ml) in response to LPS while it enhanced B-cell mitogenesis at lower concentrations (50 and 100 mg/100 ml). Purified Hp had no effect on monoclonal, antigen-specific (BSA) mitogenesis. Rabbit alveolar macrophages produced significant amounts of prostaglandin E in vitro in response to LPS but Hp had no effect on this production. However, Hp alone caused approximately the same amount of stimulation of PGE production by alveolar macrophages as did LPS alone. The ability of Hp to modulate lymphocyte as well as macrophage function seems to indicate that Hp plays a role in the moderation of inflammation. This ability to moderate inflammation, especially in the lungs, may play an important role in regulating tissue damage and disease following inhalation of inflammatory aerosols.

Polymorphism of human haptoglobin and its clinical importance

“…Haptoglobin is a powerful suppressor of lymphocyte function, as shown by its ability to inhibit the mitogenic response of lymphocytes to phytohemagglutinin and concanavalin A (Baseler and Burrell, 1983). Different T helper (Th) lymphocyte subtypes, known as Th1 and Th2 cells, are responsible for inducing and regulating the cellular and humoral immune response, respectively.…”

Haptoglobin and the Th1/Th2 balance: hints fromin vitroandin vivostudies

“…1 Hp inhibits the respiratory burst and the rise in intracellular calcium in neutrophils following fMLP stimulation. 2 It also suppresses lectin-and lipopolysaccharide (LPS)-induced proliferation of T lymphocytes and B-cell mitogenesis, 1,[3][4][5][6] and modulates macrophage function. 3 However, the mechanism of action of Hp on the immune system remains enigmatic.…”

“…2 It also suppresses lectin-and lipopolysaccharide (LPS)-induced proliferation of T lymphocytes and B-cell mitogenesis, 1,[3][4][5][6] and modulates macrophage function. 3 However, the mechanism of action of Hp on the immune system remains enigmatic. Our group has identified the promiscuous Mac-1 leukocyte β2-integrin (CD11b/CD18) as a receptor for Hp on monocytes, macrophages, granulocytes, NK cells, and small sub-populations of CD8 + T lymphocytes and B lymphocytes.…”

Human serum haptoglobin is toxic to Plasmodium falciparum in vitro

“…Crisis form parasites fail to develop properly within the erythrocyte, appearing as atypical rings or young trophozoites devoid of haemozoin [20], whereas the haptoglobin-treated parasites are affected during the trophozoite maturation phase. 8 We are currently investigating the mechanism of P. falciparum toxicity of haptoglobin. Initially it was thought that haptoglobin might act in the intracellular environment; whereas haptoglobin is an antioxidant and neutralises the potentially toxic effects of haemoglobin at physiological pH, at pH < 5.5 haptoglobin enhances the peroxidase activity of haemoglobin [21].…”

“…In recent years haptoglobin has been found to have various other functions, e.g. inhibition of prostaglandin synthesis [5], promotion of angiogenesis [6], antibody-like agglutination of Streptococcus pyogenes strains carrying the membrane antigen, T4 [7], inhibition of lectin-induced lymphocyte transformation, mediated by binding to 2 CD22 [8], promoting Thl-dominant T cell responses, possibly mediated via CDllb [9] and inhibition of the respiratory burst by phagocytes, mediated via CDllb [10].…”