Thomas Ternowitz

15-Hydroxyeicosatetraenoic Acid (15-HETE) Specifically Inhibits LTB4-Induced Chemotaxis of Human Neutrophils

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase (15-LO) product of arachidonic acid has the potential to inhibit leukotriene formation. In the present study the effect of 15-HETE on leukotriene B4 (LTB4)-induced polymorphonuclear leukocytes (PMN) and monocyte chemotaxis was investigated. LTB4-induced chemotaxis of PMNs was inhibited in a dose-dependent manner by 15-HETE. Maximum inhibition (68%) occurred at a 15-HETE concentration of 10(-4) M. The 15-LO product of eicosapentaenoic acid (15-HEPE) was approximately 10 times less potent in inhibiting LTB4-induced PMN chemotaxis. LTB4-induced chemotaxis of monocytes was unaffected by both 15-HETE and 15-HEPE. Using N-formyl-methionyl-leucyl-phenylalanine (FMLP) and complement split product C5a as chemoattractants, 15-HETE did not decrease PMN chemotaxis. Furthermore, 15-HETE itself did not affect random migration of leukocytes. The present results demonstrate that 15-HETE inhibits LTB4-induced chemotaxis of PMNs in vitro in a specific and selective way. Because 15-HETE not only inhibits formation, but also the effect of LTB4, it may be important in regulating LTB4-induced inflammation.

Frequency of skeletal disease, arthro-osteitis, in patients with pustulosis palmoplantaris

Fourteen randomly selected patients with pustulosis palmoplantaris were examined to determine the frequency of skeletal involvement. Symptoms and both clinical and radiographic signs of skeletal disease occurred in five patients (36%). Four patients had erosive and/or sclerotic changes in the region of the sternoclavicular, the first sternocostal, and/or the manubriosternal joint, in two with additional ossification of the costoclavicular ligament. Two patients had spinal involvement, one paravertebral ossifications, and the other sequelae of anterior spondylodiskitis. Peripheral joint complaints without radiographically detectable erosions, but with periarticular new bone formation, occurred in three patients. The skeletal changes are probably not incidental and seems to constitute a seronegative spondyloarthropathy associated with pustulosis palmoplantaris.

ETAF/Interleukin-1 and epidermal lymphocyte chemotactic factor in epidermis overlying an irritant patch test

We have previously demonstrated that the epidermal content of the lymphocyte activating peptide ETAF/IL‐1 and lymphocyte chemotactic factor (ELCF) increases during the development of a cellmediated immune reaction, represented either by the tuberculin skin reaction or by a positive patch test in patients with contact allergy. The present study describes the epidermal content of these mediators during an irritant patch test reaction. The results show that ELCF, but not ETAF/IL‐1, is significantly increased in the epidermis of an irritant patch test with 3% SLS or 5% croton oil, irrespective of the intensity of the clinical patch test reaction. We observed that simple occlusion of epidermis did not induce ELCF activity in healthy persons, whereas patients with previous or current eczema had a significant release of ELCF following such occlusion. These results seem to indicate that there exist important functional differences between allergic and irritant patch test reactions with respect to the presence of lymphocyte activating signals in epidermis.

Monocyte and neutrophil chemotaxis in psoriasis: Relation to the clinical status and the type of psoriasis

Chemotactic activity of purified monocytes and polymorphonuclear leukocytes was studied in fifty patients with psoriasis vulgaris and in forty-five healthy individuals by an objective in vitro assay with the use of a 51Cr-labeling technic. Both monocytes and polymorphonuclear leukocytes showed a statistically significant increase in chemotactic response, which was positively correlated with disease activity but not with the extent of the cutaneous lesions. The chemotactic activity of monocytes correlated with that of polymorphonuclear leukocytes in the same patients. Exacerbation of psoriasis was preceded by a rapid increase of polymorphonuclear leukocyte chemotaxis, and a decline of chemotaxis occurred during clinical improvement. The psoriatic leukocytes were 22% more sensitive than normal leukocytes to leukotriene B4 than to N-formyl-methionyl-leucyl-phenylalanine. Psoriatic plasma showed chemotaxis-enhancing properties, but only in patients with widespread cutaneous lesions. Additionally, monocyte and polymorphonuclear leukocyte chemotaxis was studied in twenty patients with pustular psoriasis and in fifteen patients with psoriatic arthritis. The chemotactic profiles in pustular psoriasis were different from those in psoriasis vulgaris. Patients with pustular psoriasis had significantly higher polymorphonuclear leukocyte chemotaxis than patients with psoriasis vulgaris, but the chemotactic activity of monocytes was normal. The presence of seronegative arthritis had no influence on chemotactic activity of psoriatic leukocytes.

Epidermis and lymphocyte interactions during a tuberculin skin reaction

SummaryForty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.Forty-one persons were tested for tuberculin skin reactivity. Epidermal cells (ECs) were isolated from the tuberculin reaction and from a contra lateral, non injected skin area. We found a significant increase of epidermal thymocyte activating factor (ETAF) in epidermis overlying a positive tuberculin reaction together with an increase of OKT6 and class II (HLA-DR) positive cells. Allogeneic lymphocytes proliferated significantly more when mixed with ECs from a positive tuberculin skin test. Injection of tuberculin per se or a negative reaction did not induce similar changes. The described model seems useful for functional studies of ECs and lymphocytes in patients with contact dermatitis.

Chemotactic lipoxygenase products in sera from patients with psoriasis

SummarySera obtained from 12 patients with moderate to severe psoriasis were investigated for the presence of arachidonate lipoxygenase metabolites using reverse-phase high-performance liquid chromatography after extraction on silicic acid columns. Peaks which co-chromatographed with standards of synthetic leukotriene B4 (LTB4) were collected, and the material was tested for chemotactic activity. In the sera of 5 of the patients, chemotactic activity was demonstrable in these ‘LTB4’ peaks. Although minor peaks cochromatographing with LTB4 were found in control sera, none of them contained chemotactic material. Isolated monocytes from the psoriasis patients showed enhanced chemotactic activity as compared to monocytes obtained from healthy controls. The results of our study support the view that abnormal 5-lipoxygenase activity is present in psoriasis. Further investigation is required to determine whether LTB4 is released from circulatory leukocytes or the skin.

Recombinant Human Tumour Necrosis Factor β (Lymphotoxin) Lacks Chemotactic Activity for Human Peripheral Blood Neutrophils, Monocytes, and T Cells

Human recombinant tumour necrosis factor β (rhuTNFβ)/lymphotoxin was tested for human neutrophil granulocyte (PMN), monocytes (MO), and T‐cell chemotactic activity by means of a modified Boyden chamber system. Over a wide range of concentrations (10‐7‐10‐14 M) rhuTNFβ showed no chemotactic activity for PMN, MO, or T cells. In contrast, strong chemotactic migration was elicited in PMN and MO with the tripeptide N‐formyl‐methionyl‐leucylphenylalanine (FMLP) and in T cells when complement split product C5a and leukotriene B4 (LTB4) were used as chemotaxins. The results of this study indicate that rhuTNFβ/lymphotoxin is not a chemotaxin for human PMN, MO, or T lymphocytes in vitro.

Epidermal Mediators for Lymphocytes in Contact Eczema

A total of 56 persons were studied for the presence of epidermal mediators in tuberculin skin tests, allergic patch tests, or irritant reactions from sodium lauryl sulphate (SLS) 3%. Epidermis was obtained with the suction blister technique, homogenized, dialysed, and ultrafiltered, leaving substances larger than 3 kDa for further studies. The epidermal homogenate was assayed for interleukin-1 (IL-1) activity and for the presence of epidermal lymphocyte chemotactic factor (ELCF). Our results show that simple occlusion of the skin in non-eczematous persons does not induce any significant amount of mediators. However, if the person in question suffers from irritant eczema, then occlusion per se will induce a significant amount of ELCF, but not IL-1. Both mediators are induced following a cell-mediated immune reaction in the skin irrespective of the presence of eczema. In patients with cutaneous allergy, the mediators are expressed in normal-looking, non-tested skin, when an allergic patch test is applied elsewhere. This may in part explain the excited skin syndrome.

Description of an Epidermal Lymphocyte Chemotactic Factor Which Specifically Attracts OKT4‐Positive Lymphocytes

Defibrinated venous blood was separated on Isopaque Ficoll gradients. The cells were washed and mixed with anti-CD4 (OKT4) and anti-CD8 (OKT8) monoclonal antibodies. Separation was done using fluorescence-activated cell sorting following which the cells were washed, resuspended in RPMI-1640 with 10% human A serum, and left unstimulated at 37OC for 2 days. They were then labelled with chromium-51 and adjusted to a final concentration of 3.5 x lo6 cells/ml.