CD69-null mice protected from arthritis induced with anti-type II collagen antibodies

CD69, known as an early activation marker antigen on T and B cells, is also expressed on platelets and activated neutrophils, suggesting certain roles in inflammatory diseases. In order to address the role of CD69 in the pathogenesis of arthritis, we established CD69-null mice. CD69-null mice displayed a markedly attenuated arthritic inflammatory response when injected with anti-type II collagen antibodies. Cell transfer experiments with neutrophils, but not T cells or spleen cells, from wild-type mice into CD69-null mice restored the induction of arthritis. These results indicate a critical role for CD69 in neutrophil function in arthritis induction during the effector phase. Thus, CD69 would be a possible therapeutic target for arthritis in human patients.     

Identification and Subcellular Localization of Neuronal Calcium Sensor-1 (NCS-1) in Human Neutrophils and HL-60 Cells

Secretion in neutrophils is thought to be regulated in different ways for the different granule types. Specific granules are endowed with proteins which are related to docking and fusion events and are absent on azurophilic granules. Furthermore, even if secretion of content from all neutrophil granules is a Ca(2+)-dependent process, a higher concentration of cytosolic calcium is required for azurophilic than for specific granule secretion. In this paper we show that human neutrophils and promyelocitic cells express neuronal calcium sensor-1 (NCS-1), a calcium binding protein involved in exocytosis in various cell types. Both mRNA and protein were found in mature cells and precursors. NCS-1 is shown to be mainly associated with azurophilic granules and, therefore could play an instrumental role in the calcium-dependent secretion of azurophilic granules.     

Human defensins

Antimicrobial peptides are small, cationic, amphiphilic peptides of 12–50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free -helices, extended cysteine-free -helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and -sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the -defensins, -defensins and the recently described -defensins. Mammalian -defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian -defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human -defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known -defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.J.J. Schneider and A. Unholzer contributed equally to this work     

Fate of odontoblasts and blood capillaries in the incisal region of the rat incisor pulp

Transmission electron microscopy of thin sections of the rat incisor pulp revealed that in the middle region of the incisor there were fenestrated capillaries in the “predentinal plexus” and that this region contained the tallest odontoblasts. The odontoblasts gradually became shortened in the incisal part of this region: the fenestrated capillaries in the predentinal plexus changed to continuous type capillaries. Almost all the odontoblasts had degenerated near the incisal end of the tooth. The predentinal plexus disappeared in this region, but the “subodontoblastic capillary plexus” persisted. In a specific region just beneath the worn incisal end, numerous macrophages and polymorphonuclear neutrophils appeared and scavenged the degenerating cells, possibly including the odontoblasts. © 1993 Wiley-Liss, Inc.     

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils

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Identification of Exocytosis Mediator Proteins in Peripheral Blood Neutrophils of Patients with Chronic Myeloid Leukemia

We demonstrated expression of plasma membrane proteins (syntaxin-4 and syntaxin-6) and specific/gelatinase granule membrane proteins (SNAP-25 and VAMP-2) in the peripheral blood neutrophils of patients with chronic myeloid leukemia. VAMP-1 associated with membranes of azurophilic and specific/gelatinase granules was absent in peripheral blood neutrophils of patients with chronic myeloid leukemia. Decreased capacity of neutrophils to exocytosis in chronic myeloid leukemia is probably caused by the absence of VAMP-1 in these cells.     

Nitric oxide mediates the inhibition of neutrophil migration induced by systemic administration of LPS

To investigate the role of NO in the inhibition of neutrophil migration by circulating endotoxin, mice were pretreated with NO synthase inhibitors or with a free radical scavenger (D-penicillamine), before intravenous LPS injection. LPS dose-dependently inhibited the thioglycollate-induced neutrophil migration into the peritoneal cavities. Aminoguanidine, a selective inducible NO synthase inhibitor, abolished the inhibition of neutrophil migration and the increase in serum nitrate levels induced by a nonlethal dose of LPS. During lethal endotoxemia aminoguanidine partially abolished the neutrophil migration inhibition. Additionally, D-penicillamine prevented the inhibition of neutrophil migration caused by LPS. However, Nitro-L-Arginine, a selective constitutive NO synthase inhibitor, did not prevent neutrophil migration inhibition. Aminoguanidine treatment did not affect the systemic increased levels of TNF-, IL-1, and IL-10, suggesting that NO is the final mediator involved in the inhibition of neutrophil migration. Our results suggest that NO released by the inducible NO synthase mediates the inhibition of neutrophil migration mediated by circulating LPS.     

Seasonal allergic conjunctivitis is accompanied by increased mast cell numbers in the absence of leucocyte infiltration

Background Seasonal allergic conjunctivitis (SAC) is the most common allergic disease to affect the eye. occurring alone or in association with allergic rhinitis. Infiltration with mast cells and eosinophils is characteristic of the chronic forms of allergic conjunctivitis such as vernal and atopic keratoconjunctivitis. and these cell types also contribute significantly to allergic inflammation in the skin. Indirect evidence for a similar pattern of cellular events in SAC comes from studies which demonstrate raised eosinophil and neutrophil numbers in conjunctival scrapings and elevated levels of mast cell tryptase in tears following allergen challenge. Objective To directly characterize the inflammatory cell infiltrate in SAC and to determine its clinical relevance. Methods We employed specific immunohistochemical staining to count masi cells, eosinophiis and neutrophiis in the conjunctival epithelium and lamina propria of eight atopic patients with SAC in, and 12 SAC patients out of the hay fever season. Sixteen patients with no history of ocular allergy were used as control subjects. Results Mast cells were absent from normal epithelium. During the pollen season median mast cell numbers in the lamina propria were found to be increased by 6I'J(in patients with SAC compared with normals (P= 0.012). Eosinophils were found in the lamina propria in less than half of the symptomatic patients with SAC and in only three patients were eosinophils present in the epithelium. The neutrophil numbers in the lamina propria of patients with SAC tended to be higher than normals but these changes did not reach statistical significance. Conclusion Conclusion These data based on the direct assessment of conjunctival tissue provide evidence that symptoms occur in SAC in the absence of detectable recruitment of eosinophils or neutrophils. This suggests that this disorder is related to mast cell-mediated changes.     

Neutrophil mobilization and clearance in the bone marrow

The bone marrow is the site of neutrophil production, a process that is regulated by the cytokine granulocyte colony‐stimulating factor (G‐CSF). Mature neutrophils are continually released into the circulation, with an estimated 10 11 neutrophils exiting the bone marrow daily under basal conditions. These leucocytes have a short half‐life in the blood of ～6·5 hr, and are subsequently destroyed in the spleen, liver and indeed the bone marrow itself. Additionally, mature neutrophils are retained in the bone marrow by the stromal cell‐derived factor (SDF‐1α)/chemokine (C‐X‐C motif) receptor 4 (CXCR4) chemokine axis and form the bone marrow reserve. Following infection or inflammatory insult, neutrophil release from the bone marrow reserve is substantially elevated and this process is mediated by the co‐ordinated actions of cytokines and chemokines. In this review we discuss the factors and molecular mechanisms regulating the neutrophil mobilization and consider the mechanisms and functional significance of neutrophil clearance via the bone marrow.     

丹参提取物对氧自由基引起的化学发光的抑制作用

观察了经调理的酵母多糖（ＯＺ）、Ｎ－ｆｏｒｍｙｌｍｅｔｈｉｏｎｙｌ－Ｌｅｕｃｙｌ－ｐｈｅｎｙｌａｌａｎｉｎｅ（ｆＭＬＰ）Ｃａｌｃｉｕｍ ｉｎｏｐｈｏｒｅ（Ａ２３１８７），等几种白细胞激动剂引起的大鼠腹腔中性粒细胞（ＰＭＮｓ）的化学发光和次黄嘌呤－黄嘌呤氧化酶系统（ＨＯ－ＸＯ）产生的化学发光。观察到了具有抗炎作用的中药单体７６４－３对ＰＭＮ吞噬ＯＺ引起的化学发光及ＨＯ－ＸＯ系统产生的化学发光具有明显