Vaskulitis pada Lupus Eritematosus Sistemik

AbstrakLupus Eritematosus Sistemik (LES) merupakan penyakit autoimun kompleks yang menyerang berbagai sistem tubuh. Salah satu manifestasi LES adalah vaskulitis, yaitu inflamasi pada dinding pembuluh darah. Vaskulitis sekunder akibat LES terjadi pada beberapa pasien LES dengan gambaran yang bervariasi. Gambaran vaskulitis yang tersering pada LES adalah vaskulitis kutaneus. Dilaporkan seorang perempuan 26 tahun yang telah dikenal dengan LES, datang dengan keluhan bintik-bintik merah di kedua tungkai dan lengan yang tidak gatal dan tidak nyeri. Dilakukan biopsi pada lesi kulit dengan hasil tampak pada jaringan kulit dengan epidermis yang mengalami atrofi, hyperkeratosis, ketotik plague, terdapat daerah dengan penebalan membrana basalis. Dibawah dermis tampak sebukan sel radang perivasikuler, terdapat limfosit dan beberapa leukosit PMN. Gambaran tersebut sesuai dengan gambaran discoid lupus erythematosus dan vaskulitis. Discoid lupus erythematosus merupakan salah satu bentuk dari lupus eritematosus kutaneus dan merupakan bentuk yang tersering. Pada kasus ini vaskulitis muncul menunjukkan kambuh atau aktifnya penyakit LES yang telah diderita pasien selama 2 tahun. Hal tersebut ditunjukkan dengan jumlah skor MEX SLEDAI 6 dan skor SLEDAI 12. Pasien diberikan terapi dengan metil prednisolon intravena 2x125 mg selama 3 hari serta hidroksiklorokuin 1x200 mg per oral. Respon yang baik terlihat pada hari rawatan keenam dengan berkurangnya manifestasi vaskulitis secara signifikan.Kata kunci: lupus eritematosus sistemik, vaskulitisAbstractSystemic lupus erythematosus (SLE) is a complex autoimmune disease involving many systems in one’s body. One of SLE manifestations is vasculitis, an inflammation of the vessel wall. Secondary vasculitis caused by SLE happened in few SLE patients with various manifestations. The most common SLE vasculitis is cutaneous vasculitis. It has been reported a female patient (26 years old) who was known with SLE, with red spots on both her legs and arms without feeling itchy or painful. Skin biopsy was done to the patient and the result was an appearance in skin tissue with the atrophic epidermis, hyperkeratosis, ketotic plague, thickening area of membrana basalis. In dermis underneath, was distributed inflammation cells perivascular, with lymphocyte and numerous PMN leukocyte. This appearance corresponds with discoid lupus erythematosus and vasculitis. Discoid lupus erythematosus is one most common cutaneous lupus erythematosus. In this case, the occurrence of vasculitis demonstrated an active disease of SLE. Disease activity was assessed with MEX SLEDAI and SLEDAI scores, which are 6 and 12 consecutively. The patient was given intravenous methylprednisolone 125 mg twice a day for 3 days and oral hydroxychloroquine 200 mg once daily. A good response was found in the sixth day with significant improvement of her skin lesions.Keywords: systemic lupus erythematosus, vasculitis

Attenuation of neutrophil-mediated myocardial ischemia-reperfusion injury by a calpain inhibitor

Calpains are ubiquitous neutral cysteine proteases. Although their physiological role has yet to be clarified, calpains seem to be involved in the expression of cell adhesion molecules. Therefore, we hypothesized that a selective calpain inhibitor could attenuate polymorphonuclear (PMN) leukocyte-induced myocardial ischemia-reperfusion (I/R) injury. We examined the effects of the calpain inhibitor Z-Leu-Leu-CHO in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Z-Leu-Leu-CHO (10 and 20 μM, respectively) significantly improved left ventricular developed pressure (LVDP) ( P< 0.01) and the maximal rate of development of LVDP ( P< 0.01) compared with I/R hearts perfused without Z-Leu-Leu-CHO. In addition, Z-Leu-Leu-CHO significantly reduced PMN adherence to the vascular endothelium and subsequent infiltration into the postischemic myocardium ( P < 0.01). Moreover, Z-Leu-Leu-CHO significantly inhibited expression of P-selectin on the rat coronary microvascular endothelium ( P < 0.01). These results provide evidence that Z-Leu-Leu-CHO significantly attenuates PMN-mediated I/R injury in the isolated perfused rat heart to a significant extent via downregulation of P-selectin expression.

Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury

Apocynin (4-hydroxy-3-methoxy-acetophenone) inhibits NADPH oxidase in activated polymorphonuclear (PMN) leukocytes, preventing the generation of reactive oxygen species. To determine if apocynin attenuates ischemia-reperfusion lung injury, we examined the effects of apocynin (0.03, 0.3, and 3 mM) in isolated in situ sheep lungs. In diluent-treated lungs, reperfusion with blood (180 min) after 30 min of ischemia (ventilation 28% O2, 5% CO2) caused leukocyte sequestration in the lung and increased vascular permeability [reflection coefficient for albumin (ςalb) 0.47 ± 0.10, filtration coefficient ( Kf) 0.14 ± 0.03 g · min−1· mmHg−1· 100 g−1] compared with nonreperfused lungs (ςalb0.77 ± 0.03, Kf0.03 ± 0.01 g · min−1· mmHg−1· 100 g−1; P < 0.05). Apocynin attenuated the increased protein permeability at 0.3 and 3 mM (ςalb0.69 ± 0.05 and 0.91 ± 0.03, respectively, P < 0.05); Kfwas decreased by 3 mM apocynin (0.05 ± 0.01 g · min−1· mmHg−1· 100 g−1, P < 0.05). Diphenyleneiodonium (DPI, 5 μM), a structurally unrelated inhibitor of NADPH oxidase, worsened injury ( Kf0.32 ± 0.07 g · min−1· mmHg−1· 100 g−1, P < 0.05). Neither apocynin nor DPI affected leukocyte sequestration. Apocynin and DPI inhibited whole blood chemiluminescence and isolated PMN leukocyte-induced resazurin reduction, confirming NADPH oxidase inhibition. Apocynin inhibited pulmonary artery hypertension and perfusate concentrations of cyclooxygenase metabolites, including thromboxane B2. The cyclooxygenase inhibitor indomethacin had no effect on the increased vascular permeability, suggesting that cyclooxygenase inhibition was not the explanation for the apocynin results. Apocynin prevented ischemia-reperfusion lung injury, but the mechanism of protection remains unclear.

P-Selectin-β2-Integrin Cross-Talk: A Molecular Mechanism For Polymorphonuclear Leukocyte Recruitment At The Site Of Vascular Damage

IntroductionPlatelets activated at the site of vascular damage play a pivotal role in polymorphonuclear (PMN) leukocyte accumulation in a growing thrombus2,3 and may substitute endothelial cells in the recruitment and migration of leukocytes through damaged vessel wall.4 Leukocytes, accumulated in a platelet thrombus, can contribute to further platelet activation5 and to increased fibrin deposition.6 These events, on the one hand, may contribute to the maintenance of vascular and tissue integrity. They may, however, play a pathogenic role in inflammatory and thrombotic disease, providing some biological plausibility to the epidemiological evidence of significant association between leukocyte count and the incidence of coronary heart disease.7,8 We shall focus our attention on the molecular mechanisms involved in the recruitment of PMN leukocytes on activated platelets as it occurs at the site of vascular damage, with particular attention to P-selectin- β2-integrin cross-talk.

"In vivo" leukocyte chemotaxis in experimental mice Schistosoma mansoni infection

The "in vivo" chemotaxis was studied in C57B1/10 mice 10, 30, 50 and 60 days after a Schistosoma mansoni infection in comparison to a control group (uninfected mice). Staphylococcal protein A was injected into a connective tissue air pouch of control and experimental mice and the leukocyte chemotaxis was counted. A decrease in polymorphonuclear (PMN) leukocyte response was found in infected mice in comparison to the control group (p<0.05). The 10 day infected mice showed a decreased PMN leukocyte response respecting the control group (p<0.05) and this finding became more evident 30 and 50 days post-infection. Although the PMN leukocyte response of 60 day infected mice increased in comparison to 50 day infected animals, it was still significantly lower the control response. The mononuclear leukocyte response was not significantly different between infected or uninfected mice.