James W. Larrick

Bio: James W. Larrick is an academic researcher from Duke University. The author has contributed to research in topics: Population & Receptor. The author has an hindex of 14, co-authored 32 publications receiving 1496 citations.

Modulation of cell surface iron transferrin receptors by cellular density and state of activation.

Abstract: This report describes investigations of plasma membrane transferring receptors on a variety of lymphoid cell lines and normal peripheral blood lymphocytes during activation and cell growth cycles. Transformed lymphoid cell lines have as many as 1,000 times the number of receptors found on normal resting lymphocytes. The number of iron transferrin receptors on continuous cell lines as well as normal human fibroblasts is down-regulated during the transition from log-phase growth to stationary plateau growth. When normal lymphocytes are transformed by mixed lymphocyte culture or mitogens, they rapidly express a 50-fold increase in the number of transferrin binding sites. This appearance of iron transferrin receptors anticipates nuclear changes during cell activation and subsequent mitosis of normal cells.

In vitro activation of a human macrophage-like cell line

Abstract: SEVERAL permanent murine macrophage-like cell lines exhibiting various macrophage-associated effector functions have been described1–3, but establishment of permanent human macrophage cell lines has been much more difficult4. Recently Sundstrom and Nilsson5 reported the establishment of a human histiocytic lymphoma cell line, U937, with macrophage characteristics. This line was further adapted to rapid growth in vitro by Lachman et al.6. During studies of major histocompatibility complex antigens on a number of human lymphoid cell lines we failed to detect Ia-like antigens (HLA-DR) on U937. Because these alloantigens have been reported to occur on early myeloid cells7 and might therefore be regarded as differentiation antigens of stem cells, an attempt was made to produce differentiation and expression of new cell surface molecules on U937. Procedures similar to those used to produce differentiation of myeloid cell lines8 and promote growth of macrophages in culture were tried. Although U937 cells failed to express Ia-like antigens they underwent remarkable morphological and functional changes. We report here that U937 can be activated by supernatants from human mixed lymphocyte cultures (MLC). Although this activation takes several forms, the findings reported here show marked augmentation of antibody-dependent cellular cytotoxicity (ADCC) against erythroid and tumour target cells.

Characterization of a human macrophage-like cell line stimulated in vitro: a model of macrophage functions.

Abstract: When cells of human macrophage-like cell line U937 are cultured in the presence of medium conditioned by mixed lymphocyte culture (MLC), PHA- or Con A-stimulated lymphocytes they demonstrate morphologic and functional characteristics of stimulation The cells become larger, their surface more villous, and the cytoplasm has increased numbers of lysosomes and phagosomes There is a marked (at least 10-fold) increase in antibody-dependent cellular cytotoxicity (ADCC) against both erythroid and tumor targets accompanied by increased expression of Fc receptors (FcR) There is also an augmentation of antibody-dependent phagocytosis Medium conditioned by unstimulated lymphocytes, a B lymphoblastoid cell line or a fibroblast cell line produce very little stimulation of U937 cells U937 cells gradually lose their increased ADCC capacity if they are washed free of conditioned medium (CM) but can be maintained in a stimulated state for long periods of time by culturing them in medium supplemented with PHA-CM at a concentration of 2% Stimulation of macrophage-like cell line U937 may provide a useful model for further study of mechanisms of macrophage cytotoxicity and its modulation by products of activated lymphocytes

A combination of a particular HLA-DPβ allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease

Abstract: COELIAC disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals1. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region2,3. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens4–8 and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire9–12. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities13–15. Here we use a new DNA-based method of HLA-DP typing16 to analyse the distribution of DPβ alleles in a group of coeliac disease patients and healthy controls. Two specific DPβ alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DPβ sequences suggests 470 that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DPβ alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQα and β alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DPβ allele are at increased risk for coeliac disease.

Establishment and characterization of a human acute monocytic leukemia cell line (THP‐1)

Abstract: A human leukemic cell line (THP-1) cultured from the blood of a boy with acute monocytic leukemia is described. This cell line had Fc and C3b receptors, but no surface or cytoplasmic immunoglobulins. HLA haplotypes of THP-1 were HLA-A2, -A9, -B5, -DRW1 and -DRW2. The monocytic nature of the cell line was characterized by: (1) the presence of alpha-naphthyl butyrate esterase activities which could be inhibited by NaF; (2) lysozyme production; (3) the phagocytosis of latex particles and sensitized sheep erythrocytes; and (4) the ability to restore T-lymphocyte response to Con A. The cells did not possess Epstein-Barr virus-associated nuclear antigen. These results indicate that THP-1 is a leukemia cell line with distinct monocytic markers. During culture, THP-1 maintained these monocytic characteristics for over 14 months.

Allergy, Parasites, and the Hygiene Hypothesis

Abstract: The increase of allergic diseases in the industrialized world has often been explained by a decline in infections during childhood. The immunological explanation has been put into the context of the functional T cell subsets known as T helper 1 (TH1) and T helper 2 (TH2) that display polarized cytokine profiles. It has been argued that bacterial and viral infections during early life direct the maturing immune system toward TH1, which counterbalance proallergic responses of TH2 cells. Thus, a reduction in the overall microbial burden will result in weak TH1 imprinting and unrestrained TH2 responses that allow an increase in allergy. This notion is contradicted by observations that the prevalence of TH1-autoimmune diseases is also increasing and that TH2-skewed parasitic worm (helminth) infections are not associated with allergy. More recently, elevations of anti-inflammatory cytokines, such as interleukin-10, that occur during long-term helminth infections have been shown to be inversely correlated with allergy. The induction of a robust anti-inflammatory regulatory network by persistent immune challenge offers a unifying explanation for the observed inverse association of many infections with allergic disorders.