기니픽에 유발시킨 피부사상균증에 대한 연구 : 병원서의 비교 및 모발침범 기전

Abstract

[한글]

피부사상균의 유성세대가 발견됨에 따라 동일균종내에 여러 종류가 포함되어 있음을 알게 되었으므로 각 균종 간 및 교배형 간의 병원성을 비교할 필요가 있다. 한편 피부사상균이 in vivo상태에서 모발을 침범하는 기전에 대한 전자현미경적 연구가 비교적 미흡한

상태이다. 저자는 피부사상균들 간의 병원성을 비교하기 위하여 Arthroderma(A.) benhamiae, A.vanbreuseghemii, Nannizzia(N.) gypsea 및 N. otae의 각각의 교배형 "+"및 "-"를 기니픽에 정량적으로 접종한 후 시간경과에 따른 임상 양상, 조직 변화 및 모발침범의 정

도를 비교하였고, 피부사상균의 모발침범 기전을 알아보기 위하여 N. otae를 기니픽 모발에 in vivo와 in vitro로 감염시킨 후 전자현미경으로 비교 관찰하여 다음의 결과를 얻었다.

1. 각 균종의 교배형에 따른 병원성의 차이는 없었다.

1) A. benhamiae "7"형과 "-"형, N. gypsea "+"형과 "-"형의 감염증사이에는 각각 임상양상, 조직변화 및 모발침범 정도에 차이가 없었다.

2) A. vanbreuseghemii "+"형 감염증에서는 "-"형 감염증에 비해 더 넓게 퍼지고 N. otae "-"형 감염증에서는 "+"형 감염증에 비해 더 빨리 퍼졌으나, 그밖의 홍반, 인설, 치유 기간 등의 임상 양상, 극세포증, 염증반응 등의 조직변화, 모발침범정도 등에서 각 균종의 교배형 간에 차이가 없었다.

2. 각 균종 간에는 병원성의 차이가 있었다.

1) A. benhamiae감염증에서는 가장 빨리 심한 염증반응을 나타내었고 접종 후 약 19일에 자연치유되어 가장 짧은 경과를 보였으며 모발 침범은 없었다.

2) A. vanbreuseghemii 감염증에서는 인설의 정도와 염증반응이 가장 경미하였고 약 57일간 지속되었으며, 모발 침범은 흔하며 분절포자의 형성은 드물었다.

3) N. gypsea감염증에서는 늦게 병변이 출현하고 24일에 소실되어 비교적 짧은 경과를 보였으며 모발침범은 적었다.

4) N. otae감염증에서는 심한 염증반응을 일으키면서 넓게 퍼져 나갔고 심한 모발침범과 분절포자의 형성을 보였으며 평균 63일 간 지속되었다.

3. In vivo 실험상 N. otae는 외측 모근초의 각질층과 내측 모근초를 통해 모낭 협부까지 내려간 후 모낭 협부 및 모낭 하부의 여러 곳에서 모소피의 변연부를 통해 모발 내부로 침범하였고, 침범시 특수한 형태의 균사는 발견되지 않았다. 모든 균사는 표피 과립층

과 모근의 각질이 형성되고 있는 부위를 향하여 자라나갔으며 후미의 균사는 표피 각질층, 외측 모근초 및 모발에서는 변성되어 소실되었고 내측 모근초에서는 분절포자를 형성하였다. 각질의 파괴는 주로 각질의 용해에 의해, 부분적으로 물리적 압력에 의해 이루어지

는 소견을 보였으나 균사의 세포질 및 인접한 각질에서 분비과립은 발견되지 않았다. 모든 각질은 파괴될 수 있었으며 모소피의 exocuticle과 A-layer가 가장 늦게 파괴되었다.

In vitro 실험상 N. otae는 모발 표면에서 fronded mycelium을 형성하여 모소피 변연부를 들추고 침범한 후 모소피와 모피질 사이에서 perforating organ을 형성하여 모피질과 모수질로 파고 들었다.

본 실험을 통해 임상적으로 완전형에 의한 분류법이 기존의 분류법보다 합리적임을 알 수 있었고 피부사상균의 모발 침범 기전에 대한 기초자료를 얻은데 큰 의의가 있다. 앞으로 각질 분해 효소에 대한 면역화학적 규명과 임상적 응용이 요구된다.

A Study of Experimental Dermatophytosis in Guinea Pigs:Comparisons of

Pathogenicities and Mechanism of Hair Invasion

Jong Soo Choi

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Sungnack Lee, M.D.)

Since the perfect states and mating types of dermatophytes were found, it was

recognized that several species of fungi had been included in single species and

that their mating behaviours were different. This suggests that these fungi may

have different pathogenicities. Also the electron microscopic findings of the

invasion of hair by dermatophytes in vivo were not completely investigated.

Experimental dermatophyte infections were induced to compare the pathogenicity of

dermatophytes and to evaluate the mechanisms of hair invasion. Guinea pigs were

inoculated with quantitated spore solutions of mating types of Arthroderma(A.)

benhamiae, A. vanbreuseghemii, Nannizzia(N.) gypsea, and N. otae. A paired

comparison was used for evaluating the pathogenicity between mating types and among

species by clinical and pathologic parameters and the frequency of hair invasion.

The hairs, infected with N. otae in vivo and in vitro, were examined with an

electron microscope for evaluation of the mechanism of hair invasion. The results

were as follows.

1. No notable differences in pathogenicity were observed between mating types,

except A. vanbreuseghemii "+" spread more widely than "-" type, and N. otae "-"

spread more rapidly than "+" type.

2. Significant differences in pathogenicity were observed among the species of

dermatophytes.

1) The lesion infected with A. benhamiae showed rapid onset, severe inflammation,

the shortest course (19 days) and no invasion of the hair shaft.

2) The lesion infected with A. vanbreuseghemii showed the mildest inflammation

and scales, a lengthy course (57 days) and frequent invasion of the hair shaft.

3) The lesion infected with N. gypsea showed late onset, relatively short course

(24 days) and rare invasion of the hair shaft.

4) The lesion infected with N. otae showed severe inflammation, a lengthy course

(63 days), frequent invasion of the hair shaft and formation of numerous

arthrospores.

3. In vivo, N. otae grew downward through the stratum corneum of the outer root

sheath and the inner root sheath. At the level of isthmus or in(prior of follicle,

hyphae invaded the hair shaft by lifting the margin of the cuticle. No specific

structure of the hyphae was fecund during hair invasion. All hyphae showed apical

growth toward newly formed keratin and the distal portions of the hyphae

degenerated in the stratum corneum and the hair shaft, or formed the arthrospores

in the inner root sheath. Keratin seemed to be destroyed by lysis and partly by

mechanical force. Evidence of enzyme secretion could not be found. Among the

keratins, the exocuticle and A-layer of the cuticle were the most resistant

structures to destruction.

In vitro, N. otae formed the fronded mycelia on the surface of the hair. By

lifting the margin of the cuticle, they invaded the subcuticle, then formed the

perforating organs, which grew vertically into the cortex and the medulla of the

hair shaft.

According to this study, it is apparent that the classification by perfect state

is clinically more suitable than that by morphology, and the mechanism of hair

invasion by dermatophytes is defined more clear. Further immunobiochemical study of

the role of keratinase in the hair invasion by dermatophytes and its clinical

applications are needed.

[영문]

Since the perfect states and mating types of dermatophytes were found, it was recognized that several species of fungi had been included in single species and that their mating behaviours were different. This suggests that these fungi may have different pathogenicities. Also the electron microscopic findings of the

invasion of hair by dermatophytes in vivo were not completely investigated.

Experimental dermatophyte infections were induced to compare the pathogenicity of dermatophytes and to evaluate the mechanisms of hair invasion. Guinea pigs were inoculated with quantitated spore solutions of mating types of Arthroderma(A.) benhamiae, A. vanbreuseghemii, Nannizzia(N.) gypsea, and N. otae. A paired

comparison was used for evaluating the pathogenicity between mating types and among species by clinical and pathologic parameters and the frequency of hair invasion.

The hairs, infected with N. otae in vivo and in vitro, were examined with an electron microscope for evaluation of the mechanism of hair invasion. The results were as follows.

1. No notable differences in pathogenicity were observed between mating types, except A. vanbreuseghemii "+" spread more widely than "-" type, and N. otae "-" spread more rapidly than "+" type.

2. Significant differences in pathogenicity were observed among the species of dermatophytes.

1) The lesion infected with A. benhamiae showed rapid onset, severe inflammation, the shortest course (19 days) and no invasion of the hair shaft.

2) The lesion infected with A. vanbreuseghemii showed the mildest inflammation and scales, a lengthy course (57 days) and frequent invasion of the hair shaft.

3) The lesion infected with N. gypsea showed late onset, relatively short course (24 days) and rare invasion of the hair shaft.

4) The lesion infected with N. otae showed severe inflammation, a lengthy course (63 days), frequent invasion of the hair shaft and formation of numerous arthrospores.

3. In vivo, N. otae grew downward through the stratum corneum of the outer root sheath and the inner root sheath. At the level of isthmus or in(prior of follicle, hyphae invaded the hair shaft by lifting the margin of the cuticle. No specific structure of the hyphae was fecund during hair invasion. All hyphae showed apical growth toward newly formed keratin and the distal portions of the hyphae degenerated in the stratum corneum and the hair shaft, or formed the arthrospores in the inner root sheath. Keratin seemed to be destroyed by lysis and partly by mechanical force. Evidence of enzyme secretion could not be found. Among the

keratins, the exocuticle and A-layer of the cuticle were the most resistant structures to destruction.

In vitro, N. otae formed the fronded mycelia on the surface of the hair. By lifting the margin of the cuticle, they invaded the subcuticle,then formed the perforating organs, which grew vertically into the cortex and the medulla of the

hair shaft.

According to this study, it is apparent that the classification by perfect state is clinically more suitable than that by morphology, and the mechanism of hair invasion by dermatophytes is defined more clear. Further immunobiochemical study of the role of keratinase in the hair invasion by dermatophytes and its clinical applications are needed.